Q2 2019 Earnings Call
Yeah.
Operator: Please stand by. Ladies and gentlemen, thank you for standing by.
Please standby.
Ladies and gentlemen, thank you for standing by welcome to the Alnylam Pharmaceuticals conference call to discuss second quarter 2019 financial results.
Operator: Welcome to the Alnylam Pharmaceuticals conference call to discuss second quarter 2019 financial results. There will be a question and answer session to follow. Please be advised that this call is being taped at the company's request. I would now like to turn the call over to the company. Please do so.
There will be a question and answer session to follow please be advised that this call is being taped at the company's request I would now like to turn the call over to the company. Please go ahead.
Good morning, I'm, Christine Lindenboom, Vice President of Investor Relations and corporate communications at on Eilam with me today on the phone are John Maraganore, Chief Executive Officer, Barry Green President Optibase now president of R&D, and the owning Chief Financial Officer, Yvonne Greenstreet, Chief operating Officer, and Jeff Fulton School in the role of Chief Financial Officer effective July 13th.
Christine Regan Lindenboom: Good morning. I'm Christine Lindenboom, Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Meriganori, Chief Executive Officer, Barry Green, President, Akshay Vaishnaw, President of R&D, Manmeet Soni, Chief Financial Officer, Yvonne Greenstreet, Chief Operating Officer, and Jeff Poulton, who will assume the role of Chief Financial Officer effective July 13th. For those of you participating via conference call, the slides that are available via webcast can also be accessed by going to the investor page of our website, www.alnylam.com.
For those of you participating via conference call. The slides that are available via webcast can also be accessed by going investor page of our website Www dot com.
Christine Regan Lindenboom: During today's call, as outlined in slide 2, John will provide some introductory remarks and provide general context, Barry will provide an update on our commercial and medical affairs progress, Akshay will review recent clinical updates, Manmeet will review our financials, Jeff will comment on some of his perspectives and priorities as our new incoming CFO, and Yvonne will provide a brief summary of upcoming milestones before we open the call to your questions. I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of a safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by those forward-looking statements as a result of various important factors, including those discussed in our most recent quarterly update on file with the FEC. In addition, any forward-looking statements represent our views only as of the date of this recording. It should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. And with that, I'll turn the call over to John.
During today's call as outlined on slide two John will provide some introductory remarks and provide general context variable will provide an update on our commercial and medical affairs progress actually will review recent clinical update Manmeet will review our financials, Jeff will comment on some of his perspectives and priorities as our new incoming CFO and avant will provide a brief summary of upcoming milestones before we open the call to your questions.
I would like to remind you that this call will contain remarks concerning alnylams future expectations plans and prospects, which constitute forward looking statements for the purposes of a safe Harbor provision the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by those forward looking statements as a result of various important factors, including those discussed in our most recent quarterly update on file with the FCC. In addition, any forward looking statements represent our views only as of the date of this recording it should not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update such statements.
And with that I'll turn the call over to John .
John Meriganori: Thanks, Christine, and thank you, everyone, for joining the call this morning. In the second quarter of 2019, we continued strong execution across both our commercial and R&D objectives. Barry will get into the details on our commercial and medical affairs progress, but at a high level, as we approach the one-year anniversary of the Ompatro launch and approval, we continue to be very pleased with the Ompatro uptake, with over 500 patients on commercial drugs at the end of the second quarter. Importantly, we continue to see opportunity for steady and continued revenue growth in the quarters and years to come, driven by new patient finding, global expansion Moreover, advancement of Phase III development activities for Petitseran and Butreseran into the entirety of hereditary and wild-type ATTR amyloidosis is expected to expand our opportunity significantly.
Thanks, Christine and thank you everyone for joining the call. This morning.
In the second quarter clean energy, we continued strong execution across both our commercial and R&D objectives.
Barry will get into the details on our commercial and medical affairs progress, but at a high level as we approach the one year anniversary of the apparel launch and approval. We continue to be very pleased with the potential uptick with over 500 patients on commercial drug at the end of the second quarter.
Importantly, we continue to see opportunity for steady and continued revenue growth in the quarters and years to come driven by new patient finding.
Global expansion in near to mid term evidence generation activities.
Moreover, advancement to phase III development activities for parties rent and Patrice ran into the entirety of hereditary and wild type HCR Assembly doses is expected to expand our opportunity significantly.
John Meriganori: And, of course, our revenue growth is not just about our ATTR program alone since we have a broader portfolio of late-stage assets, including a program in registration. We have also made excellent progress against our R&D goals. Akshay will cover this in more detail, but with positive Govoserad phase 3 results and completed regulatory submissions, we believe we're poised for approvals in the U.S. and Europe and launches of our second product early next year, assuming positive regulatory reviews. Just yesterday, we announced that the FDA has granted Gavosran a priority review with a February 4th PDUFA date and no need for an outcome.
And of course, our revenue growth is not just about our a TCR program alone since we have a broader portfolio of late stage assets, including a program new registration.
We also made excellent progress against our R&D goals, obviously will cover this in more detail, but was positive grocer as phase three results and completed regulatory submissions. We believe we're poised for approvals in the us in Europe and launches of our second product early next year, assuming positive regulatory reviews, just yesterday, we announced that the FDA has granted to go both rent a priority review with a February 4th producer date and no need for an outcome.
John Meriganori: In addition, we're now positioned for two additional phase 3 program readouts by the end of the year, starting with Inclisiran, our PCSK9 program licensed to the medicines company, which we'll read out in the next few weeks, and then Lumasiran, our wholly owned primary hyperoxyluria RNAi therapeutic program. And to enable longer-term growth in a capital-efficient manner, we completed our largest-ever partnership with Regeneron to build an industry-leading pipeline of innovative medicines focused on ocular and CNS diseases, where we see significant opportunities for RNAi therapeutics. Furthermore, with the substantial funding from our Regeneron Alliance, we believe our balance sheet has the strength to support a multi-year horizon for business execution. Based on all our commercial and R&D progress and near-term prospects, we couldn't be more excited about Alnylam today, and we believe that we have a clear line of sight toward our Alnylam 2020 goal of being a global, multiproduct, top-tier biopharma company with a deep clinical pipeline to bolster continued growth and a robust product engine to fuel future innovation, a profile rarely, if frankly ever, achieved All this sets off an incredibly important period in the Alnylam story.
In addition, we are now positioned for two additional phase three program readout by the end of the year, starting with increased around our Pcsknine program license to the medicines company, which will read out in the next few weeks and then last around our wholly owned primary Hyperoxaluria R&D I'd therapeutic program.
And to enable longer term growth in a capital efficient manner, we completed our largest ever partnership with regeneron to build an industry, leading pipeline of innovative medicines focused on modular and CNS diseases, where we see significant opportunities for Adi therapeutics.
Furthermore, with the substantial funding from our Regeneron Alliance, we believe our balance sheet as a straight to support a multi year horizon for business execution.
Based on all our commercial and R&D progress and near term prospects, we couldn't be more excited about all of them today and we believe that we have a clear line of sight toward our Alnylam 2020 goal of being a global Multiproduct top tier Biopharma company with a deep clinical pipeline to bolster continued growth and a robust product engine to fuel future innovation a profile rarely is frankly ever achieved in biotech.
All this sets up an incredibly important period in the old story.
John Meriganori: On the one hand, we believe that our modular, reproducible, and, very importantly, organic platform for innovative medicines is hard to match, where, for many reasons, we believe our return on investment exceeds industry norms. And now, having achieved the landmark approval of the first ever RNAi therapeutic and having built a global and leverageable commercial capability to generate revenue growth, we have greater confidence than ever in our ability to deliver on the commercial promise of RNAi. At the same time, we know that some of our stakeholders are eager to hear how revenue growth and continued investment in our innovative pipeline will support the path to a self-sustainable and attractive financial profile for Alnylam in the coming year. For these reasons, I'm very excited to have Jeff Poulton, our incoming CFO, join our team to help us navigate through this important transition and grow Alnylam for the future.
On the one hand, we believe that our modular reproducible and very importantly, organic platform for innovative medicines is hard to match where for many reasons. We believe our return on investment exceeds industry norms.
And now having issued a landmark approval of the first ever RDR therapeutic and having built a global and Leverageable commercial capability to generate revenue growth, we have greater confidence than ever in our ability to deliver on the commercial promise of already on.
At the same time, we know that some of our stakeholders are eager to hear how revenue growth and continued investment in our innovative pipeline will support the path to a self sustainable and attractive financial profile for LDL into the coming years.
For these reasons Im very excited to have Jeff Fulton, our incoming CFO joined our team to help us navigate through this important transition growing our model for the future.
John Meriganori: Jeff will make some comments later in the call. I'd also like to thank Manbeat Sony for everything he has contributed to our company and the foundation that we've built together to support our Alnylam 2020 aspiration. Now, before I turn the call over to Barry, I would like to mention that we are planning to hold an R&D day in New York City on the morning of Friday, November 22nd, where we will recap our latest progress in advancing our pipeline of RNAi therapeutics. We very much hope that you'll be able to join us in person or via webcast. So with that, I'll now turn the call over to Barry to review our commercial and medical affairs progress in more detail.
Jeff will make some comments later in the call I'd also like to think maybe Sony for everything he has contributed to for our company and the foundation that we've built together to support our own element 2020 aspirations.
Now before I turn the call over to Barry I would like to mention that we are planning to hold at R&D day in New York City on the morning of Friday November 22nd where we will plan to recap our latest progress in advancing our pipeline of Rnai therapeutics.
We very much hope that you'll be able to join us in person or on the webcast. So with that I'll now turn the call over to Barry to review, our commercial and medical affairs progress in more detail Barry Thanks, John and good morning, everyone.
Eric Green: Barry? Thanks, John, and good morning, everyone. I'll begin by reviewing Ampatra's commercial performance in the second quarter. We achieved $38.2 million in global Ampato Net product revenues in the second quarter. As in the first two and a half quarters of launch, the majority of revenues stem from U.S. sales, and we're now pleased, for the first time, to provide more color on the geographic split with $10 million from the EU and $28.2 million coming from the United States. As of June 30th, over 500 patients worldwide were receiving commercial on-patron treatment. We're quite pleased with the overall growth and continued global demand this quarter, even with increasing product options from recent market entrants and the availability of investigational drugs through expanded access programs and investigational clinical trials. As a reminder, there have been three sources of patients in our launch to date. Patients from our Expanded Access Program, or EAP; Patients Who Are Known to Sites and New De Novo Patients.
Ill begin by reviewing on Patters commercial performance in the second quarter.
We achieved $38.2 million in global on Petro net product revenues in the second quarter.
As in the first two and a half Kors launch majority of revenues stemming from US sales and we are now pleased for the first time to provide more color on the geographic split with 10 million from the EU and 28.2 million coming from the United States.
As of June Thirtyth over 500 patients worldwide will receive in commercial and Patrick treatment.
We're quite quite pleased with the overall growth and continued global demand this quarter, even with increasing product options from recent market entrance and the availability of investigational drugs through expanded access programs investigational clinical trials.
As a reminder, there have been three sources of patients in our in our launch to date patients from our expanded access program or EAP.
Patients, who are known to sites and new de Novo patients.
Eric Green: In the first couple of quarters of launch, we effectively captured the first two sources, and we're now very much into the de novo patient pool, particularly in the United States. Now, when we include patients in clinical trials in our global EAP, that number increases to greater than 750 patients worldwide who are now being treated with pitiserine. We believe that we're on track to have approximately 1,000 patients on Ompatro across commercial, clinical studies, and our Expanded Access Program by the year-end 2019, a very exciting milestone in our overall effort. Let me now turn to the U.S. market dynamics. On the physician front, we're seeing continued growth in both the number of new prescribers as well as repeat prescribers. In fact, over 50% of the prescriptions received in the second quarter came from new prescribers.
In the first couple of quarters of launch we effectively capture the first two sources and we are now very much into the de novo patient pool, particularly in the United States.
Now we include patients in clinical trials, and our global GDP that number increased to greater than 750 patients worldwide, who are now being treated with pretty soon.
We believe that we are on track to have approximately a thousand patients on petro across commercial clinical studies and our expanded access program by the year end 2019, a very exciting milestone in our overall efforts.
Let me now turn to the U.S market dynamics.
On the physician front, we're seeing continued growth in both the number of new prescribers as well as repeat prescribers.
In fact over 50% of the prescriptions received in second quarter came from new prescribers.
Eric Green: We believe new prescribers will continue to increase as health care provider disease awareness grows, fueled by multiple players engaged in disease state awareness and education. Regarding the mix of prescribers, we continue to see about 50% of the U.S. initial forms come from cardiologists, which we believe indicates strong recognition of the mixed phenotype and the awareness of polyneuropathy in this population.
We believe new prescribers will continue to increase that healthcare provider disease awareness grows fueled by multiple players engaged in disease state awareness and education.
Regarding the mix of prescribers, we continue to see about 50% of us start forms come from cardiologists, which we believe indicates strong recognition of the mixed phenotype and the awareness of Polyneuropathy and in this population.
Eric Green: Additionally, we're seeing greater numbers of new prescribers in specialties like primary care and hematology as disease awareness increases outside of the expert center. Positive experience from patients and health care providers with Ompatro also continues to be a highlight and, of course, is a key predictor for future use. Speed to therapy also continues to improve, and overall persistence and adherence are very strong today. Regarding U.S. market access, as reported by external coverage reports, we're very pleased that we now have confirmed access to Empacho, if prescribed, for more than 98% of U.S. lives across commercial, Medicare, Medicaid, and other government payer categories. We continue to effectively partner with U.S. payers and have avoided the payor headwinds reported in this space and often reported with orphan disease launches.
Additionally, we're seeing greater numbers of new prescribers specialties like primary care and hematology as disease awareness increases outside of the expert centers.
Positive experience for patients and Elk healthcare providers within Petro All code also continues to be a highly and of course is a key predictor for future use.
Speech therapy also continues to improve and overall persistence and adherence are very strong today.
Regarding us market access as reported by external coverage affords. We're very pleased that we now confirmed access to impact show is prescribed for more than 98% of us lives across commercial Medicare Medicaid and other government payer categories.
We continue to effectively partner with us payers have avoided the pair headwinds reported in this space and often reported with orphan disease launches.
Eric Green: We're proud of this result in a very complex U.S. market access environment and believe it reflects the constructive, collaborative, and productive approach, including the use of value-based agreements, or VBAs, we've adopted with the payer community. Now, turning to the EU, and more broadly, our Canada, Europe, Middle East, and Africa, or SEMEA region, we're very pleased with Ampatua's performance in the region As noted earlier, we achieved 10 million in EU net product revenues during the second quarter. Some notable achievements during the quarter include favorable and competitively differentiating technology assessments in Germany, France, and Italy. A highlight of the period was the achievement of pricing agreements with Nice in England and with pricing authorities in Scotland.
We're proud of this result in a very complex us market access environment and believe it reflects the constructive collaborative and productive approach, including the use of value based agreements were VVA is we've adopted with the payer community.
Now turning to the EU and more broadly, our Canada, Europe , Middle East and Africa, or CEMEA region, we're very pleased with our patches performance in the region.
As I noted earlier, we achieved $10 million Ooh net product revenues during the second quarter.
Some notable achievements during the quarter include favorable and competitively differentiating technology assessments, and Germany, France and Italy.
A highlight for the period was achieved in a pricing agreements with nice in England and with pricing authorities in Scotland.
Eric Green: We also received marketing authorization approval in Canada, where Empetra is now available for commercial use. Through direct reimbursement, name patient sales, or reimbursed expanded access, we're now selling on Patreon in over 10 countries in the Semien region. Given the timing of pricing and reimbursement discussions in SAMEA, we expect continued market access-based growth and a number of commercial on-patron patients for the rest of 2019 and into 2020. In addition to growth coming from patient finding and utilization where patients may experience inadequate response to other products for Disease Progression and Tolerability.
We also received marketing authorization approval in Canada. We're in Petro is now available for commercial use.
Through direct reimbursement named patient sales or reimbursed expanded access we're now selling on pattern over 10 countries in the CEMEA region.
Given the timing of pricing and reimbursement discussions in CEMEA, we expect continued market access base growth.
And the number of commercial and Patrick patients for the rest of 2019 and into 2020.
In addition to growth coming from patient, finding and utilization where patients may experience inadequate response.
In other for other products.
For disease progression and Tolerability.
Eric Green: Turning to our commercial progress outside the United States and SEMEA, we recently received marketing authorization approval from Ampato in Japan. We're preparing for a launch in Japan and also advancing our plans to submit for regulatory approval in Brazil while exploring non-patient sales in Latin America and other countries. Given the presence of endemic disease and a favorable reimbursement environment, we expect Japan, after the U.S., to be our second largest country in revenues and patients on drug exit in 2020. As more countries around the world come online, we expect this to be an additional driver of future growth.
Turning to our commercial progress outside the United States and CEMEA, We recently received marketing authorization approval from Patrick in Japan.
We are preparing for a launch in Japan, and also advancing our plans to submit for regulatory approval in Brazil.
While scoring exploring non nut.
Non patient sales in Latin America countries.
Given the presence of endemic disease and the favorable reimbursement environment, we expect Japan. After they use to be our second largest country in revenues and patients on drug exiting 2020.
As more countries around the world come online we expect this to be an additional driver of future growth.
Our team also remains committed to addressing the challenges of raising disease awareness and improving diagnosis.
Eric Green: Our team also remains committed to addressing the challenge of raising disease awareness and improving diagnosis in HATR amyloid doses. Improved medical education and diagnosis will help patients reach treatment options faster. The data are clear that when patients receive treatment earlier in the disease course, it improves their overall prognosis.
RM windows improve medical education, and diagnosis will help patients reach treatment options faster.
The data are clear that when patients receive treatment earlier in the disease course improves their overall prognosis.
Eric Green: Now regarding patient diagnosis, as we've highlighted previously, our Alnylam Act program, available in the U.S. and Canada, is a third-party genetic screening initiative aimed at facilitating the diagnosis of patients suspected of having HHT trauma doses. As of July, over 15,000 samples have been submitted, and over 1,000 patients with pathogenic mutations have been identified, with a sustained hit rate of 6-8%. Since there are other sponsored genetic testing programs, and HCPs also have reimbursed genetic testing, Alnylamak represents only a portion of the genetic test. We're also pleased now to partner with 23andMe to help customers of their consumer genetic service learn more about their genetic risk for the three most common TTR variants in the United States.
Now regarding patient diagnosis as we've highlighted previously our all Nile Akt program available in the Us and Canada to the third party genetic screening initiative aimed at facilitating diagnosis of patients suspected of having a determine the doses.
As of July over 15000 samples have been submitted and over 1000 patients with pathogenic mutations have been identified with the sustained hit rate of 6% to 8%.
Since there are other sponsor genetic testing programs and HCP is also reimbursed genetic testing.
Ill imac represents only a portion of the genetic testing.
We're also pleased now to part with 23 and me to help customers with their consumer genetic service learn more about the exact risk of the three most common feature variance in the United States.
In summary, within patch or achieving approval and access and more and more countries with improving diagnosis and patient finding and with continued evidenced generating efforts highlighting the differentiated features on Petro we're encouraged to see continuous and steady growth and we are confident in our future commercial potential even in an increasingly competitive environment.
Eric Green: In summary, with Ampatro achieving approval and access in more and more countries, with improved diagnosis and patient finding, and with continued evidence-generating efforts highlighting the differentiated features of Ampatro, we're encouraged to see continuous and steady growth, and we're confident in our future commercial potential, even in an increasingly competitive environment. As I previously mentioned, with more companies in the ATTR amyloidosis market, we believe overall awareness will continue to accelerate, and we're enthusiastic about the benefits this will confer on patients. Moreover, as we look at the broader time horizon, we believe there are significant growth opportunities for our overall ATTR franchise, including through potential label expansion for Ampatro and both hereditary and wild-type ATTR amyloidosis patients with cardiomyopathy, and also with the advancement of Utrusiran, our once-quarterly sub-Q investigational RNA therapeutic into potentially all segments of the ATTR amyloidosis
As I previously mentioned with more companies in the eight TTR amyloidosis market. We believe overall awareness will continue to accelerate and were enthusiastic about the benefits this will convert to patients.
Moreover, as we look at the broader time horizon. We believe there are significant growth opportunities for our overall eight TTR franchise.
Including through potential label expansion from Petro and both regulatory and Wild type 80, chairman dose patients with cardiomyopathy and also with the advancement of nutrition are once quarterly sub Q investigational rnai therapeutic into potentially all segments of the CRM windows market.
Eric Green: We're very committed to being the leaders in ATT in Midosa's space, and we believe our efforts position us well in the future. Finally, let me briefly turn to Govosran, which is now under active review by both U.S. and European regulators. Assuming positive decisions by both agencies, we expect VOTUS RAM to launch in the U.S. and SMEA in early 2020.
We're very committed to being leaders in 80 generally doses space and we believe our efforts position us well in the future.
Finally, let me briefly turn to gross rent, which is now under active review by both us and European regulators.
Assuming positive decisions by both agencies, we expect to close rate will launch in the us and CEMEA in early 2020.
Eric Green: In the meantime, we're leveraging the capabilities built from PASRO launch and commercialization and following the best practices developed country by country. Our team is focused on improving awareness and diagnosis of acute hepatic porphyria in the healthcare professional and patient communities and laying the groundwork for a successful launch. As part of these overall efforts, we've launched our AIP Physician and Patient-Focused websites to give patients resources and education materials about their disease and to provide healthcare professionals with content and tools to help them recognize the signs and symptoms of AHP and to help them navigate through the appropriate tests to arrive at an accurate diagnosis. Through the Alnylam Act, we provide access to genetic testing at no charge for individuals in the U.S. or Canada who may carry While this program for AHP is in the early stage, we can report 479 tests submitted and 51 patients with AHP mutations as of July, accounting for approximately 10% of the hit rate.
In the meantime, we're leveraging the capabilities build from Petro launch and commercialization and following the best practices developed country by country. Our team is focused on improving awareness and diagnosis of acute hepatic porphyria and the HCP and patient communities.
And laying the groundwork for a successful launch.
As part of these overall efforts, we've launched our ASP physician and patient focused websites to patients give patients resources and education materials about their disease.
And for eight Cps with content and tools to help them recognize the signs and symptoms of HP.
And to help them navigate through the appropriate tests to arrive at an accurate diagnosis.
Through all now Max and provide access to genetic testing at no charge for individuals to us or Canada, who may carry a gene mutation known to be associated with HP.
While this program for HP is in the early stage. We can report 400, Sevenx has submitted and 51 patients with HP mutations.
As of July accounting for approximately 10% hit rate.
Eric Green: There is a very clear unmet need and significant burden of disease in acute hepatic porphyria. Assuming positive regulatory reviews, we're very excited about a new treatment option we can bring to patients and the associated commercial opportunity for Duvosaran. We look forward to the possibility of delivering this medicine to AHP patients early next year. As we have said in the past, it's our belief that this can be an attractive, ultra-rare orphan disease opportunity with over $500 million in global peak revenue potential. As with Umpatro and other orphan drug launches in under-diagnosed populations, we expect DeVos grants to show a consistent and steady pattern of revenue growth after launch. With that, I'll now turn it over to Akshay to review our recent R&D and pipeline progress. Akshay. Thanks, Barry.
There is a very clear unmet need and significant burden of disease and acute hepatic porphyria, assuming positive regulatory reviews, we're very excited with the new treatment option, we can bring to patients and the associated commercial opportunity for Davos room.
We look forward to the possibility of delivering this medicine to HPP patients early next year.
As we've said in the past, it's our belief that this to be attractive ultra rare orphan disease opportunity with over $500 million global peak revenue potential.
As with them patio and other orphan drug launches in under diagnosed populations. We expect both strengths show consistent steady pattern of revenue growth after launch.
With that ill now turn over to Akshay to review, our recent R&D and pipeline progress auction I am sorry, and good morning, everyone.
Akshay K. Vaishnaw: Thanks, Barry, and good morning, everyone. In the interest of time, I'm going to limit my prepared remarks to our multiple phase III clinical programs. We'll have a richer opportunity to touch on our broader pipeline later in the year at R&D Day, as John mentioned earlier. Let me start with Patisaran, which is the unbranded name for Ompatra.
In the interest of time, Okay to live in my prepared remarks, our multiple phase three clinical programs will have a rich opportunity to touch on our broader pipeline later in the year at R&D day, as Joe mentioned earlier.
Let me start with piece around which is the unbranded name from Patrick.
Akshay K. Vaishnaw: At the Peripheral Nerve Society meeting in June, we presented new 12-month interim results from the ongoing Global Open Label Extension Study of PetitSERAN showing sustained improvement in neuropathy impairment and quality of life for patients after 13 months of treatment. These promising new results also show the importance of treating patients as early as possible to minimize the advancement of disease. The newly presented data also, in our view, showed what we believe to be a continued and favorable differentiation profile for ptetusseran, including results in patients who experienced progression on tofamidase prior to initiating treatment with ptetusseran. With the caveat, of course, that there'll be no head-to-head studies comparing petition plan with other agents.
As the peripheral nerve society meeting in June we presented new 12 month interim results from the ongoing global open label extension study all parties ran showing sustained improvement in europes, the impairment and quality of life for patients after 13 months of treatment.
These promising new results also show the importance of treating patients early as possible to minimize advancement of disease.
The new digs ex data also in have you showed what we believe to be a continued favorable differentiation profile folk piece ran including results in patients who experienced professionals comedies price initiating treatment with season.
With the caveat of course that there being no head to head studies, comparing the Tucson with operations.
Akshay K. Vaishnaw: We now look forward to advancing the evaluation of Petitseran in the Apollo B Phase 3 study, aimed at expanding the Onpatra label to include cardiomyopathy in both the inherited and wild-type ATTR amyloidosis market. We're on track to start this study later this year, and if positive, we will seek regulatory support for an expanded label for Pritestrand in the 21 to 22 timeframe. As you know, we're also advancing food Triceram, which is delivered by a quarterly subcutaneous injection and is also in development for AT-carotidosis. While we've been enrolling HAT care patients with polyneuropathy in the ongoing Helios A Phase III study with Beatrice Rand, we're pleased to announce today that we've obtained regulatory alignment on the design of Helios B. Helios B will be a The primary endpoint will evaluate Futrisrat's impact on cardiovascular hospitalization and mortality. For comparative reasons, we'll await providing further details until the study starts later this year.
We now look forward to advancing the evaluations designed in the Apollo phase three study.
Aimed at expanding the old Patra label to include Cardium ops, the comparative in wild type TTR amyloidosis market.
We're on track to solve this study later this year and if positive we will seek regulatory support for expanded label for Patisiran in the 21 to 22 timeframe.
As you know we're also advancing through trips around which is delivered by quarterly subcutaneous injection and it will say development for a tablet doses.
While we have been enrolling HCT patients with Polyneuropathy and the ongoing Healios a phase three study with fortress. Ron we are pleased to announce today that we have obtained regulatory alignment on the design of Helio speed.
Hello, Steve will be a phase three study open interest trends in enhancing the quality of 80 tablet as patients with cardiac milestones.
The primary endpoint will evaluate butros trends impact on cardiovascular hospitalizations and mortality.
For competitive reasons, we await providing further details until the studies off later this year.
Akshay K. Vaishnaw: If successful, Helios B should allow Nutrition RAN to enter the very large wild-type AD family doses market opportunity with clinical outcomes data. Now, let's move on to Qvostrat, our Investigational RNAi Therapeutic in Development for the Treatment of Acute Hepatic Porphyria. In April, we presented complete positive results from the ENVISION phase 3 study. The first round demonstrated a robust treatment effect in significantly reducing the annualized rate of composite attacks in AHP patients compared to placebo. Specifically, Givosran met the primary efficacy endpoint with a 74% mean and 90% median reduction relative to placebo in the Agilized Rate of Composite Porphyria Attacks in patients with AIP over 6 months. Turning to safety and tolerability results, AEs were reported in 89.6% of U.S. transplant patients and 80.4% of placebo patients in the pivotal study. Serious adverse events were reported in 20.8% of KiloSharan patients and 8.7% of the placebo group, or patients with a divorce or unarmed, as previously mentioned, discontinued treatment due to an AED. Three SAEs in the Gibb-Ostrand Group were reported as related to study drug, a single case each of pyrexia, abnormal liver function tests, and chronic kidney disease.
If successful in aerospace should allow lutron to end to the very large wall Taipei details later as this market opportunity with clinical outcomes data.
Let's move on to give us ramp our investigational rnai therapeutic in development for the treatment of acute medical fares.
In April we presented the complete posted results from the envisioned phase three study.
If I was trying to demonstrate to robust treatment effect and significantly reducing the annualized rate of composite attacks in HIV patients received placebo.
Specifically give us on met the primary efficacy endpoint with ascent strokes and mean at 90% median reduction relative to placebo in the annualized rate component both for attacks in patients with IP over six months.
Turning to safety and Tolerability results AIDS, our reported 99.6% of give us on patients and 8.4% of placebo patients in the pivotal study.
Serious adverse events were reporting 20.8% of QSR on patients and 8.7 of the placebo group.
For patients with the restaurant ALM as previously mentioned discontinued treatment due to an eight.
Three assays in the restaurant group were reported as it related to study drug a single case each of pyrexia abnormal liver function test as chronic kidney disease.
Akshay K. Vaishnaw: We were very pleased in the second quarter to complete the rolling submission of the NDA with the US FDA and to submit the MA with the European Medicines Agency. And we announced just yesterday that both applications have now been accepted and that the FDA has granted a priority review setting an approval date of February 4, 2020. The FDA has also indicated that they do not foresee a need for an advisory committee meeting at this time.
We were very pleased in the second quarter to complete the rolling submission of the NDA with the USA FDA and to submit the M.A. with the European Medicines Agency.
And we announced just yesterday that both applications are now being accepted and that the FDA has gone to the project review setting a PDUFA date of February full 2020 .
The FDA has also indicated that they do not foresee a need for an advisory committee meeting at this time.
Finally, with respect to base rent. We've now enabled an expanded access program to potentially make your restaurant available to qualified HP patients falling requests from healthcare providers.
Akshay K. Vaishnaw: Finally, with respect to KibosRAN, we've now enabled an expanded access program to potentially make KibosRAN available to qualified AHP patients following requests from healthcare providers. I'll now turn to recent progress with Lumastran, an investigational RNAi therapeutic in development for treatment of primary hyperoxylurea type 1, or PH1. At the Oxalosis and Hyperoxyurea Foundation meeting in June, we presented final results from a Phase I-II study and interim data from a Phase II OLE study of lumastra. In these studies, we continue to see robust learning of urinary oxalate to normal or near-normal levels and an encouraging tolerability profile. As you know, we're now conducting the Illuminate A Phase 3 study on your mouse right now. Randomized, Double Blind, Serial Control Study, MPH-1 Patients Ages 6 or Older with Mild to Moderate Renal Impairment.
I'll now turn to recent progress with the mass ramp investigational rnai therapeutic in development for the treatment of primary Hyperoxaluria type one or ph one.
At the outflows in Hyperoxaluria Foundation meeting in June we presented final results from a phase one two study an interim data from the phase two early study over the mass strategy.
In these studies, we continue to see robust letters of urinary oxalate to normal or near normal levels and an encouraging tolerability profile.
As you know we're now conducting they live in a phase three study off Umass right. This is a randomized double blind placebo controlled study mph lung patients ages, six or older with mild to moderate renal impairment.
We completed enrollment in this pivotal trial and remain on track to report topline results from ILLUMENATE eight in late 2019, and a positive to submit regulatory filings beginning in early 2020.
Also in the second quarter, we initiate dilute into may be a phase three study of new mass around NPS from patients under the age of six we plan to start the third phase three trial in new macys intangible in patients with severe renal impairment late to this year.
Akshay K. Vaishnaw: We have completed enrollment in this pivotal trial and remain on track to report top-line results from Illuminate A in late 2019 and, if positive, to submit regulatory filings beginning in early 2020. Also, in the second quarter, we initiated Illuminate B, a phase 3 study of Lumasaran in PH1 patients under the age of 6. We plan to start the third phase 3 trial, Illuminate C, in PH1 patients with severe renal impairment later this year. In addition to progress we've made with our wholly owned late-stage assets, our partners at the medicines company and at Sanofi have also been advancing our partner phase 3 assets. In May, the medicines company reported interim results from the ongoing Orion 3 early study of Inclisran and the Investigational RNAi Therapeutic Tablet PCFK9, demonstrating sustained lowering of LDL cholesterol by more than 50%, with no material safety issues observed in the study.
In addition to progress we've made with our hotel in late stage assets our partners at the medicines company and that Sanofi has also been advancing our positive phase three ounces in May the medicines company reported interim results from the ongoing arrived three of these studies include surrounded investigational rnai therapeutic targeting pcsknine, demonstrating sustained lowering of LDL cholesterol by more than 50% with no material safety issues observed in the study.
We now look forward to seeing topline results from the inquest ran around 11 that nine and then 10 pivotal study starting in the second half of the third quarter.
And I am encouraged by the more than 3500 patient years of safety data from the phase three program that have been reviewed on seven separate occasions by the independent data monitoring committee with no recommended changes to study conduct notably this is the largest human experience for an investigational rnai therapeutic.
And positive results if achieved will be an important milestone for the entire field.
Akshay K. Vaishnaw: We now look forward to seeing top-line results from the InclisRAN in around 11, then 9, and then 10 pivotal studies starting in the second half of the third quarter and have been encouraged by the more than 3,500 patient years of safety data from the Phase III program that have been reviewed on seven separate occasions by the Independent Data Monitoring Committee with no recommended changes to study conduct. Notably, this is the largest human experience for an investigational RNA therapeutic. All of these positive results, if achieved, will be an important milestone for the entire field. So with that, let me now turn the call over to Munmi to review our financials. Munmi?
So with that let me now turn the call that made to review our financials, let me.
Thanks, Eric and good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter of 2019.
I would like to take this opportunity to provide a brief overview of three key areas, our cash position, our second quarter 2009 results and our updated 2019 financial guidance.
Let me start with our cash balance we ended the second quarter with a strong balance sheet off approximately $1.97 billion in cash cash equivalents marketable securities and restricted investments.
Manmeet Soni: Thanks Akshay and good morning everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter of 2019. I would like to take this opportunity to provide a brief overview of three key areas, our cash position, our second quarter 2019 results, and our updated 2019 financial guidance. Let me start with our cash balance. We ended the second quarter with a strong balance sheet of approximately $1.97 billion in cash, cash equivalents, marketable debt securities, and restricted investments. Our cash balance includes proceeds of $800 million received in the second quarter attributed to our REGION RON collaboration.
Our cash balance includes proceeds off $800 million.
Well received in the second quarter attributed attributed to our Regeneron collaboration.
Moving now to our revenues total second quarter revenues were $44.7 million, we recorded $38.2 million off on back on our product global revenue during the second quarter of 2019, which represents 45% growth from first quarter net product global revenues of $26.3 million.
Our global roster met our GTN or so days during the second quarter of 2019 was in mid Twentys.
Cost of goods sold was $4.3 million for the second quarter, which is approximately 11% as a percentage of net product revenues.
Manmeet Soni: Moving now to our revenues, total second quarter revenues were $44.7 million. We recorded $38.2 million of Onpatro Net Product global revenue during the second quarter of 2019, which represents 45% growth from first quarter Net Product global revenues of $26.3 million. Our global gross to net, or GTN, percentage during the second quarter of 2019 was in the mid-20s. Cost of goods sold was $4.3 million for the second quarter, which is approximately 11% as a percentage of net product revenues. We recognized $6.5 million of collaboration revenue during the second quarter of 2019 as compared to $29.9 million during the second quarter of 2018. As expected, the decrease in collaboration revenues is primarily due to a decrease in reimbursable activities in connection with our collaboration agreements with Sanofi Genzyme and Weave.
We recognized $6.5 million of collaboration revenue during the second quarter of 2019 as compared to $29.9 million during the second quarter of 2018.
As expected the decrease in collaboration revenues is primarily due to a decrease in reimbursement activities in connection with our collaboration agreements with Sanofi Genzyme and Weve.
Moving to other operating costs and expenses.
GAAP R&D expenses were $163.9 million for the second quarter of 2019 as compared to $137.6 million for the second quarter of 2018.
non-GAAP R&D expenses were $148.6 million as compared to $126 million for the second quarter of 2018.
The increase in non-GAAP R&D expenses was due to increased license fees related to our collaboration agreement with Regeneron and increased compensation expenses and facility expenses as a result of growth in the number of our late stage programs and higher headcount and clinical trial expenses during the period as we continued to expand and advance our development pipeline.
Manmeet Soni: Moving to other operating costs and expenses, GAAP R&D expenses were $163.9 million for the second quarter of 2019 as compared to $137.6 million for the second quarter of 2018. Non-GAAP R&D expenses were $148.6 million as compared to $126 million for the second quarter of 2018. The increase in non-GAAP R&D expenses was due to increased license fees related to our collaboration agreement with Region RON and increased compensation expenses and facility expenses as a result of growth in the number of our late-stage programs and higher headcount and clinical trial expenses during the period as we continue to expand and advance our development pipeline. This increase was offset by a decrease in manufacturing expenses related to reduced patches of drug substance and raw materials.
This increase was offset by a decrease in manufacturing expenses related to reduce patches of drug substance and raw materials.
Turning to achieving GAAP pension expenses were $104.8 million as compared to $84.7 million for the second quarter of 2018.
non-GAAP operating expenses were $97.4 million as compared to $74.1 million for the second quarter of 2018.
The increase in non-GAAP operating expenses was due primarily to an increase in commercial and medical affairs headcount in connection with the continued global launch of on backdrop.
Manmeet Soni: Turning to SG&A, GAAP SG&A expenses were $104.8 million, as compared to $84.7 million for the second quarter of 2018. Non-GAAP SG&A expenses were $97.4 million, as compared to $74.1 million for the second quarter of 2018. The increase in non-GAAP SG&A expenses was due primarily to an increase in commercial and medical affairs headcount in connection with the continued global launch of On Patrol. We are pleased today to have updated our 2019 Annual Non-GAAP R&D Expense Guidance to be in the range of $550 to $575 million compared to our previously guided range of $550 to $590 million. We are also pleased to have tightened our 2019 Annual Non-Gap SG&E Expense Guidance to be in the range of $390 to $400 million, as compared to our previously guided range of $390 to $410 million.
We are pleased today to have updated our 2019 annual non-GAAP R&D expense guidance to be in the range of $550 million to $575 million compared to our previously guided range of $550 million to $590 million.
We are also pleased to have tightened our 2019 annual non-GAAP pension expense guidance to be in the range of $390 million to $400 million as compared to our previously guided range of $390 million to $410 million.
Finally on a personal note today is my last earnings call with online and team are thoroughly enjoyed my time as part of the team and I am proud of the many contributions made to the launch of the company as a commercial enterprise and supports global expansion across multiple geographies.
I'm confident that the foundation created over the past few years will serve as an item well for many years to come I've also enjoyed working with Jeff Gordon on the CFO transition.
I will now hand, it over to Jeff to highlight some of his perspectives Jeff.
Thanks for me and thanks for your help in the transition I'd like to make just a few brief remarks as I prepare to formally assume the CFO role next week.
Manmeet Soni: Finally, on a personal note, today is my last earnings call with the Alnylam team. I have thoroughly enjoyed my time as part of the team, and I am proud of the many contributions made to the launch of the company as a commercial enterprise and support its global expansion across multiple geographies. I am confident that the foundation created over the past few years will serve Alnylam well for many years to come. I've also enjoyed working with Jeff Poulton on the CFO transition. I will now hand it over to Jeff to highlight some of his perspectives. Okay, Jeff?
I'm very excited to be joining our line loan at this stage and its growth as it establishes its global commercial operations from early and plus compressed with El Nio UBS technology and team and the company has potential to make a difference in patients lives with this new frontier medicine.
Strongly believed that with its first commercial product today prospects for many more commercial products in the coming years, beginning in 2020, and a deep clinical pipeline and robust organic product engine for the future. Our nylon is positioned to emerge as a top tier buyer furnished so cynical company consistent with John's earlier comments, a key focus for me will be working with my new colleagues to create a roadmap the financial self sustainability is on island becomes a successful global commercial organization with significant topline growth fueled by a deep R&D pipeline I look forward to this challenge and communicating our plans in the future.
Jeff Poulton: Thanks, Bunmeet, and thanks for your help in the transition. I'd like to make just a few brief remarks as I prepare to formally assume the CFO role next week. I'm very excited to be joining Alnylam at this stage in its growth as it establishes its global commercial operation. I'm really impressed with Alnylam's technology and team and the company's potential to make a difference in patients' lives with this new frontier of medicine. I strongly believe that with its first commercial product today, prospects for many more commercial products in the coming years, beginning in 2020, and a deep clinical pipeline and robust and organic product engine for the future, Alnylam is positioned to emerge as a top-tier biopharmaceutical company. Consistent with John's earlier comments, a key focus for me will be working with my new colleagues to create a roadmap to financial self-susta I look forward to this challenge and communicating our plans in the future. With that, I'll now turn the call over to Yvonne to review our goals for the remainder of the year. Yvonne?
With that ill now turn the call over to move on to review our goals for the remainder of the year avant.
Thanks, Jeff and welcome to the team we couldn't be happier to have you on board.
I'm really thrilled with the progress we've made in 2019, so far so we still have a number of exciting milestones to look forward to the remainder of the year.
The starters, we plan to continue our global commercialization upon Patrick including launching in Japan and other countries.
We also look forward to initiating the Apollo phase three study in mid 2019.
Yvonne L. Greenstreet: Thanks Jeff, and welcome to the team. We couldn't be happier to have you on board.
Aimed at securing and expanded commercial label for the T. strength to include wild type and hereditary cardiac amyloidosis.
Yvonne L. Greenstreet: I'm really thrilled with the progress we've made in 2019 so far, but we still have a number of exciting milestones to look forward to in the remainder of the year. For starters, we plan to continue our global commercialization of Onpatro, including launching it in Japan and other countries. We also look forward to initiating the Apollo B Phase III study in mid-2019, aimed at securing an expanded commercial label for patisserin to include wild-type and hereditary cardiac amyloidosis. For vitreceram, we plan to continue enrolling the Helios A Phase III trial throughout the year and expect to initiate Helios B, an outcome study, in wild-type and hereditary ATTR cardiac amyloido With Govosran, we plan on having additional data from Ambition presented at the ICPP meeting in early September.
With the trees ranch, we plan to continue enrolling the hideous a phase three trial throughout the year and expect to initiate Tds be an outcome study in wild type and hereditary eight TTR cardiac amyloidosis patients in late 2019.
With converse Ryan we plan on having additional data from ambition presented at the IC Pp meeting in early September .
Turning to the mess around with enrollments in the eliminate a phase three study now complete we plan to report topline results from that study in late 2019.
We will also continue enrolling pediatric patients in the Navy and plan to start the eliminate C study in P.H., one patients with severe renal impairment later in 2019.
Yvonne L. Greenstreet: Turning to Lemacaran, with enrolment in the Illuminate A Phase 3 study now complete, we plan to report top-line results from that study in late 2019. We will also continue enrolling pediatric patients in Illuminate B and plan to start the Illuminate C study in PH1 patients with severe renal impairment later in 2019. With Inclisiran, we expect our partners at the medicines company to report top-line results from the Orion 9, 10, and 11 studies beginning later this quarter, and assuming positive data, to submit an NDA for Inclisiran by the end of the year. And, of course, we'll continue advancing our pipeline of earlier-stage clinical efforts, as well as exciting preclinical efforts, and we'll highlight those milestones throughout the rest of In particular, you should expect data readouts from a number of our early- and mid-stage clinical programs. Let me now turn it back to Christine to coordinate our Q&A session. Christine?
Within Cleese ran we expect our partners at the medicines company to report topline results from the Airlines 910, and 11 studies beginning later this quarter and assuming positive data to submit an MD a friend cleese ramp by the end of the year.
And of course, we'll continue advancing our pipeline of earlier stage clinical efforts as well as exciting preclinical assets and will highlight those milestones throughout the rest of the year as they occur in particular, you should expect data readouts from a number of our early and mid stage clinical programs.
Let me now turn it back to Christine to coordinate our Q and a session Christine.
Thank you Yvonne operator, we will now open the call for questions to those out then we would like to ask you to limit yourself to one question each and I get that next year. If you have additional questions.
Thank you if you'd like to ask a question. Please signal by pressing star one on your telephone keypad.
If you are using a speaker phone. Please make sure. Your mute function is turned off to allow your signal to reach our equipment.
Christine Regan Lindenboom: Thank you, Yvonne. Operator, we will now open the call for questions to those who have filed in. We would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.
Once again its star one to ask a question.
Our first question is from L. Steele young from Cantor Fitzgerald.
Operator: Thank you. If you'd like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Once again, it's star 1 to ask a question. Our first question is from Althea Young from Cantor Fitzgerald.
Hey, guys. Thanks for taking my question and congrats on the progress as you continue this launch I'm just one from me maybe I have a follow on question, but can you just talk a little bit about stamatis and what you're seeing and hearing from how doctors make decisions like if you present. Your doctor Cardio is and then you know just kind of tagging on to that can you talk a little bit more about how the presence of both down this drug and the Pfizer drug can have driven diagnosis can you give any quantitative metrics or is there any other color you can give us around that thanks.
Eric Green: Hey guys, thanks for taking my question, and congrats on the progress as you continue this launch. Just one for me, maybe, and it has a little bit of a follow-on twist, but can you just talk a little bit about tetamotus and what you're seeing and hearing from how doctors make decisions since, like 50% of your doctors are cardios, and then, you know, just kind of tagging on to that Can you talk a little bit more about how the presence of both the onus drug and the Pfizer drug could have driven diagnosis? Can you give any quantitative metrics, or is there any other color you can give us around that?
Great. Thanks, Lydia Barry you want to handle that yeah. So let's see we've done on the emerging landscape is too early to give specifics around increase diagnosis and increased speed of diagnosis other than the color that.
We are gaining more and more new prescribers.
Every quarter, which is a sign that new people are learning about disease seeing the disease, and then are comfortable diagnosing and holding on to their patients. So you anecdotally, we're definitely seeing increase awareness and having multiple players and every cardiology Congress educate that theres that there is a disease of 80 terminally dose has certainly been helpful for patients and raising awareness.
Eric Green: Great. Thanks, Alethea. Barry, do you want to hand it over?
Eric Green: Jerry, you want to handle this? Yeah, so, Alicia, on the emerging landscape, it's too early to give specifics around increased diagnosis and increased speed of diagnosis, other than the color that we are gaining more and more new prescribers every quarter, which is a sign that new people are learning about the disease, seeing the disease, and then are comfortable diagnosing and holding on to their patients. So, you know, anecdotally, we're definitely seeing an increase in awareness, and having multiple players at every cardiology congress educate that the disease of ATTR amyloidosis has certainly been helpful for patients in raising awareness. Now, you know, to find out more specifically, again, it's too early in the launch to understand the particular dynamics.
No.
On to founded specifically again, it's too early in the launch to understand the particular dynamics, what our market research is telling us is that physicians, who understand hereditary TTR amyloidosis, even in those mixed phenotype with Polyneuropathy I'm Petros the drug of choice, particularly United States and then.
For those that are wild so clearly to them is a choice in Europe were to feminists has been present for number of years physicians understand the progression of the business and were seeing a number of patients that are switched hereditary patients from to families onto on Petro in the major markets where does the news.
Eric Green: What our market research is telling us is that physicians who understand hereditary ATTR amyloidosis, even in those with a mixed phenotype with polyneuropathy, Ompatro is the drug of choice, particularly in the United States. And then, for those that are wild-type, clearly, Tefaminis is a choice. In Europe, where Tefaminis has been present for a number of years, physicians understand the progression of Tefaminis, and we're seeing a number of patients that are switched, hereditary patients, from Tefaminis onto Ompatro in the major markets where Tefaminis has been used. Does that answer your question, Alethia?
So does that answer your question Lydia.
Yes. Thanks.
Great. Thank you.
Well go next to Gina Wang from Barclays.
Thank you for taking my questions first one also regarding that.
Patch or commercial.
A question for over 500 patients come I should talk how many were from X.U.S. and also falling Lsds question, 49% demand from cardiologist How's the payer coverage for these patients.
Eric Green: Yes, thanks.
John Meriganori: Great, thank you.
Great. Let me, let me quickly address the first one and then I'll hand, it over to Barry for the second one we're not breaking out patient numbers by region. We are for the first time breaking out.
Eric Green: We'll go next to Gena Wang from Barclays. Thank you for taking my questions. First one, regarding the Ompatra commercial question. For over 500 patients on commercial drugs, how many were from the ex-U.S.? And also, following Alicia's question, 49% demand from cardiologists. How's the payer coverage for these patients?
Revenues and reported 28.2 billion in the U.S. and 10.
In in rest of world semi in this case.
So that's that's a portion where we limited for really competitive reasons, Barry you want to answer the second question.
John Meriganori: Great. Let me quickly address the first one, and then I'll hand it over to Barry for the second one.
Yeah in terms of in terms of us payer coverage, which reported I mean, we remarkably have external reports.
Eric Green: You know, we're not breaking up patient numbers by region. But we are, for the first time, breaking out revenues, and we're reporting $28, point two million in the US and ten in the rest of the world, you know, in this case. So that's that's unfortunate. We're going to limit it for really competitive reasons. Barry, do you want to ask the second question?
Saying that 98% of our patients who have prescribed on patch will be reimbursed and Petro is actually quite remarkable we have not to date had a patient rejected by a pair.
Just to add to that Gina were.
The very strong belief that the proactive and.
Hi quality approach that we took in engaging with payers as we introduced Patrick to the market.
John Meriganori: Yeah, in terms of U.S. payer coverage, which we reported, I mean, we remarkably have external reports saying that 98% of our patients who, if prescribed Umpetro, will be reimbursed for it. It's actually quite remarkable. We have not, to date, had a patient rejected by a payer.
And continue to have discussions with payers even to this day around value based agreements. These are all elements of what has I think been a very successful market access story for this important medicine to the us market.
John Meriganori: And I, you know, just to add to that, Gena, we're of the very strong belief that the proactive and, you know, high-quality approach that we took in engaging with payers as we introduced Onpatra to the market and continue to have discussions with payers, even to this day, around value-based agreements. These are all elements of what has, I think, been a very successful market access story for this important medicine in the US market. Thank you.
Thank you.
And moving on our next question will come from Whitney Ijem from Guggenheim.
Hey, guys. Thanks for taking the question on the first one I guess I'm going to ask them on both ends of the first one in terms of the greater than 500 million for development opportunity any color you can give us on what that assumes in terms of use and sporadic versus recurrent patients either kind of in terms of how the drug will be used or or relative breakdown of patients in either bucket.
Eric Green: And moving on, our next question will come from Whitney Egem from Guggenheim. Hey guys, thanks for taking the questions. The first one, I guess I'm going to ask them about Gewozran. So the first one, in terms of the greater than $500 million for Gewozran opportunity, any color you can give us on what that assumes in terms of
Sure Great question.
Maybe just for the benefit of others on the call obviously, the recurrent patient population.
That that we have estimated.
To be approximately a thousand patients in the us in Europe and they are about.
Transcription Error: Transcribed by https://otter.ai
Estimated to be 5000 patients with sporadic disease defined as three attacks or less.
Transcription Error: or the relative breakdown of patients in either bucket.
Eric Green: Sure, great question. Maybe just for the benefit of others on the call, obviously, the recurrent patient population that we have estimated to be approximately 1,000 patients in the U.S. and Europe, and there are about, you know, estimated to be 5,000 patients with sporadic disease defined as three attacks or less. So keep in mind that, you know, any patient that experiences an attack can experience an attack that can be life-threatening. So it doesn't, you know, lessen the importance of their disease if they are a sporadic patient. But with that, Barry, do you want to comment a little bit about how, you know, we get to the belief set around a $500 million opportunity?
Keep in mind that.
Any patient that experience as an attack can experience attack that can be life threatening so it doesn't lessen.
The importance of their disease is there a sporadic patient.
But with that Barry do you want to comment a little bit about how we get to the believes that around a written the 500 million dollar opportunity.
Yes, John John you outlined it very very well as with many ultra rare orphan diseases, where patient journeys can last 13 to 15 years and patients show up with three to four unnecessary surgery or mis diagnosed by about a dozen.
Physicians in their journey, we believe that there are probably many more patients than the number that John highlighted out there.
As interesting fact, as little as three years ago, the Porfirio consortium, which is setting the disease for 20 years did not have the benefit of an industry partner doing natural history by working with them. We've all now understood that two thirds of patients experienced debilitating chronic pain between index. So as John said, it's not just about the attack rate number of attacks. It's about the overall devastating nature of the disease. So when you take the 1000 5000 likely a growing and.
Eric Green: Yeah, and John, you outlined it very, very well. As with many ultra-rare orphan diseases where patient journeys can last 13 to 15 years and patients show up with three to four unnecessary surgeries or are misdiagnosed by about a dozen physicians in their journey, you know, we believe that there are probably many more patients than the numbers that John highlighted out there. As an interesting fact, as little as three years ago, the Porphyria Consortium, which has been studying this disease for 20 years, did not have the benefit of an industry partner doing natural history. And by working with them, we've all now understood that two-thirds of patients experience debilitating chronic pain between attacks. So, as John said, it's not just about the attack rate and number of attacks.
And multiply that by.
An orphan price point, we think there is a very significant opportunity now of course, we're going to take the same proactive nature.
Driven by our patient access philosophy.
With grocer as we've taken with Petro and we'll be very proactive with payers to ensuring we put the right value based agreements in place so that patients in the United States and frankly around the world have access to an important medicine for their devastating disease.
Great and one quick follow up on patch or any color you can give on the relative to actually use price average that you asked at this point.
Eric Green: It's about the overall devastating nature of the disease. So, when you take the 1,000 and 5,000, likely a growing number, and multiply that by, you know, an orphan price point, we think there's a very significant opportunity. Now, of course, we're going to take the same proactive nature driven by our patient access philosophy with Devoster as we did with Patro, and we'll be very proactive with payers to ensure we put the right value-based agreements in place so that patients in the United States, and frankly around the world, have access to an important medicine for their devastating disease.
Yes, Barry you want to comment as well as the big swing as we highlighted on previous calls we've held the price spend very very tight on a per vial basis, and then of course.
Price varies because it is weight based dosing so in countries with bigger people, it's more dollars per patient per year and smaller people, it's less but the vile price is very very tight.
Thanks.
Thank you Whitney.
Well go next to on new Palm Rama from JP Morgan.
Hey, guys. Thanks, so much for taking my question and congratulations on all the progress here.
Eric Green: Great. And one quick follow up on Patro. Any color you can give on the relative?
In looking at.
In the U.S. like you've outlined here, you're getting about 80% of the on Patrick demand coming from cardiologist wondering if you could provide any color on some of the U.S. prescribing trends and then maybe any color on the gating factor to starting healios to be for the two strength. Thanks. So much.
Eric Green: XUS price versus U.S. at this point.
Eric Green: The U.S. at this point.
Eric Green: Yeah, Barry, do you want to comment?
Eric Green: Thanks, Whitney. As we've highlighted on previous calls, we've held the price band very, very tight on a per vial basis, and then, of course, price varies because it is weight-based dosing, so in countries with bigger people, it's more dollars per patient per year, and in smaller people, it's less, but the vial price is very, very tight.
Great. So lets have Barry talk little bit about the ex us trends of prescribers.
Eric Green: Thank you, Ernie.
And then Akshay you can handle the next the second question so Barry.
Akshay K. Vaishnaw: We'll go next to Anupam Rama from J.P. Morgan. Hey guys, thanks so much for taking the question and congratulations on all the progress here.
Yes, Thanks, Anna as you highlighted.
We said about 50% from the US prescribers are cardiologist and interestingly enough. The number of additional spera specialties, including primary care physicians nurse practitioners is growing a real sign that as a health care providers become familiar with the disease the patient they understand how to diagnose and clearly what's prescribed at least in our case with on Petro.
Akshay K. Vaishnaw: In the U.S., as you've outlined here, you're getting about 50% of the Onpatra demand coming from cardiologists. I'm wondering if you could provide any color on some of the O.U.S. prescribing trends and then maybe any color on the gating factors for starting Helios-B for Vitustram. Thanks so much.
Eric Green: Great, so let's have Barry talk a little bit about the XUS trends for prescribers, and then Akshay you can handle the next, the second question. Okay, Barry.
Ex us it really depends on the country. There are some countries like France that are better.
Eric Green: Thanks Anupam. As you highlighted, we said about 50% of U.S. prescribers are cardiologists, and interestingly enough, the number of additional specialties, including primary care physicians, and nurse practitioners, is growing. A real sign that as healthcare providers become familiar with the disease, see a patient, they understand how to diagnose and clearly what to prescribe, at least in our case with Onpatro. In XUS, it really depends on the country. There are some countries, like France, that are highly coordinated with centers, and there are named centers where a neurologist or cardiologist takes care of those patients. And then in places like Germany, it's primarily neurology-driven. So, you know, it really depends, XUS, on the country and how the centers are established. Turning to Japan, which we mentioned earlier, we believe that the primary prescribers, at least in the initial launch in Japan, will be neurologists because those are the folks that manage the overall disease symptomology. Now, of course, the dynamic back in the United States really is the V122I patient population. So in parts of the world where there are patients of Western African descent, we probably will see a bigger uptake in cardiology, at least in a hereditary space.
Highly coordinated with centers and their named centers, where a neurologist or cardiologist.
Takes care of those patients and in places like Germany is primarily neurology driven so.
It really depends ex us on the country and how the centers are established turning to Japan, which we mentioned earlier, we believe that the primary prescribers at least the initial launch in Japan will be neurologists because those are the folks that manage the overall disease Symptomology now of course.
Dynamic back to United States really is the V. One to two why patient population. So in parts of the world where patients of our of Western African descent, we probably will see a bigger uptake in cardiology at least in the hereditary space.
Just following up on if I'm following up on the DSP question.
Essentially the main gating factor was getting aligned with Rick.
Excuse me getting aligned with regulatory agencies globally, and I think we're in great shape now as we reported this morning. So we're looking forward to a vigorous thoughts about program in the second half this year now and as you know, we know will detail sites globally.
And we're excited to start growing wild type patients as well of course in that study.
Does that answer your question.
Right, yes, great. Thanks for taking my question.
Thank you.
Ritu Baral from Cowen has our next question.
Good morning, everyone. Thanks for taking my question I've already gotten a few emails this morning on some concerns around.
And you asked specific growth I think the assumption is that the Q1 number.
Akshay K. Vaishnaw: Just following up on the Helios B question, essentially the main gating factor was getting aligned with the regulatory agencies globally, and I think we're in great shape now as we reported this morning, so we're looking forward to a vigorous start for that program in the second half of this year now, and as you know, we know all the TTL sites globally, and we're excited to start enrolling in wild-type patients as well, of course, in that study.
Uh huh.
Q1 revenue number of 26.3 was largely.
95% driven by by Us.
You know understanding you don't want to comment on patient numbers can you give us.
A little more comfort around the us growth rate.
Akshay K. Vaishnaw: Does that answer your question?
Can you comment on how things like Helios a enrollment.
Akshay K. Vaishnaw: or ask your own questions.
Manmeet Soni: Thank you.
Manmeet Soni: Ritu Baral from Cowen has our next question. Good morning everyone, thanks for taking my question.
How much of an impact that's having on the launch and things like persistence, a little more color on persistence of treatment.
John Meriganori: I've already gotten a few emails this morning on some concerns around specific U.S. growth. I think the assumption is that the Q1 number, the Q1 revenue number of 26.3, was largely 95% driven by the U.S. Although you don't want to comment on patient numbers, can you give us a little more comfort around the U.S. growth rate? Can you comment on things like Helios A enrollment, how much of an impact that's having on the launch and things like persistence, a little more color on persistence of treatment, especially given the steroid pretreatment?
Especially given that the steroid free treatment.
Yes, rich to first of all I mean.
The concern about US road is completely wrong actually.
We've had steady growth in the us and Europe , maybe you want to comment more specifically to provide good provide support for the sure Sean So they do as as John mentioned, we had consistent growth that you saw the global revenue grew over approximately 45% from Q1 to Q2.
But if I split out us and Europe use was going even higher end use was growing at a 50% rate from Q1 to Q2, so to give you numbers, which would not bid and you would see them in the 10-Q filing when you file later today this evening or tomorrow.
John Meriganori: Yeah, Ritu, first of all, I mean, the concern about U.S. growth is completely wrong, actually. We've had steady growth in the U.S. and in Europe. Mamie, do you want to comment more specifically to provide support for that?
For Us last quarter Q1 was approximately $18.8 million and this quarter is 28, so that shows a pretty strong.
Got a 50 person in Europe , we were last quarter at $7.5 million and now. This is this quarter was $10 million and not also shows a 33% growth, but as you know there are in Europe . The growth comes primarily as we launch new countries and because of the final pricing.
Manmeet Soni: Sure, sure, John. As John mentioned, we had consistent growth. As you saw, global revenue grew by approximately 45% from Q1 to Q2, but if I spread out the U.S. and Europe, the U.S. was growing at an even higher rate. It was growing at a 50% rate from Q1 to Q2. So, to give you numbers which were not there, and you would see them in the 10Q filing when we file later today, this evening, or tomorrow, for the U.S., our last quarter, Q1, was approximately $18.8 million, and this quarter is 28. So, that shows a pretty strong growth of 50%. In Europe, we were last quarter at $7.5 million, and now this quarter is $10 million. So, that also shows 33% growth.
Imbursement finalized so it's it as steady and John mentioned, we are showing the steady and continuous growth in our living and there is no concern on the pool, you as Europe and global revenue growth.
Hi, just to give on that sorry, Yes go ahead no Barry if there were some more cushions on persistence on adherence, yes, I mean, I think you covered the growth incredible and just to emphasize we are seeing continues its steady growth in United States and believe it will continue maybe even a particular uptake in the in the out quarters.
Manmeet Soni: But as you know, in Europe, growth comes primarily as we launch new countries and we get the final pricing and reimbursement finalized. So, as Barry and John mentioned, we are showing steady and continuous growth in our revenue, and there is no concern for both U.S., Europe, and global revenue growth. I just want to give on – sorry. Yeah, go ahead.
Because of awareness in Europe is going to be highlighted.
We're in countries were launched we continue to see growth and a number of new countries will come on late this year into 2020.
And then Japan is coming on late this year and into 2020. So we do see a new market entrants and then within each country steady growth within countries. So that dynamic will continue.
Manmeet Soni: I'm sorry. Yeah, go ahead.
You asked about you asked about continuation, we see tremendous continuation of patients on on Petro anecdotally, we hear tremendous reports about physician experience and patient experience and the adherence rate remains very very high it's still what way early into our lawn to give specific numbers, but it remains very high and just to follow up on that great too.
Eric Green: Yeah, I mean, I think you covered the growth. It's incredible. And just to emphasize, we are seeing continuous and steady growth.
Eric Green: Outcourters because of awareness. In Europe, as Mameed highlighted, where countries were launched, we continue to see growth, and a number of new countries will come on line late this year and into 2020. And then Japan is coming on late this year and into 2020. So we do see a new market entrance, and then within each country, steady growth within each country. So that dynamic will continue. You asked about its continuation. We see tremendous continuation of patients on Patro. Anecdotally, we hear tremendous reports about physician experience and patient experience, and the adherence rate remains very, very high. It's still too early into our launch to give specific numbers, but it remains very high.
The Apollo study itself, the very low dropout rate there the high conversion rate to the only persistence in the early there is little evidence.
That the risk benefit is being well tolerated in patients.
Our staying on drug we know from OTI patients who've been on drug from 2013 14 on what's actually from the original phase two and then the phase III, we're five years into it.
So this fairly common I don't think.
Akshay K. Vaishnaw: And just to follow up on that, Ritu, the Apollo study itself, the very low dropout rate there, the high conversion rate to the only treatment, the persistence in the only treatment, this is all evidence that the risk-benefit is being well-tolerated, and patients are staying on drugs. We know from only patients who've been on drugs from 2013-14 onwards, actually, from the original phase two and then the phase three, we're five years into it, so this steroid comment I don't think applies, and we have very good evidence now that patients are tolerating the steroid pre-regimen well, which, by the way, over the years, the dose has been considerably reduced.
Applies and we have very good evidence accumulating now book patients. So tolerating the steroid free regimen, well, which by the way over the years as the dose would be considerably reduced as well.
Does that answer your question we do.
The objective healios today on that as well on the lunch enrollment of helium say on the yes, I mean look I mean, as we said from the beginning obviously he'll USA patients are potential on Petro patients we know that.
And there are there for every patient that goes the helio say they could be a commercial patient of course, we understand that.
Akshay K. Vaishnaw: That ends your question, Ritu.
But we're investing in that program for the benefit of having a new product offerings for patients in the future in the not too distant future that we think will continue to drive growth of the franchise. So it is obviously a very.
Operator: Executive Helios A.
Operator: Transcribed by https://otter.ai
Operator: I mean, look, I mean, as we said from the beginning, obviously, Helios A patients are potential Patro patients. We know that. And, you know, they're there. For every patient that goes into Helios A, they could be a commercial patient. Of course, we understand that. But we're investing in that program for the benefit of having a new product offering for patients in the future and in the not too distant future that we think will continue to drive growth of the franchise. So it is, you know, obviously, a very eyes wide open type of decision to do that. Now, we are, importantly, expanding, you know, just this past quarter significantly into sites outside the US. And, you know, we are going to see the benefit of that in countries and markets where there is no reimbursement at the present time. So that, you know, will obviously dilute any, you know, effect that might occur in the commercial on Patro growth from clinical studies.
Eyes wide open type of decision to do that now we are importantly, expanding.
You know just this past quarter significantly at the sites outside the us and.
We are good to see the benefit of that.
In countries and markets, where there is no reimbursement at the present time, so that will obviously do not Eddie.
Attacked.
That might occur on the commercial on Petro.
Growth from clinical studies.
Got it Super helpful and that was already three questions I'll get back in the queue before Josh comes from me Gray Bridget. Thank you if you're Lucky day.
Well take our next question from Paul Mathias from Stifel.
Hi, This is net on for Paul Thanks for taking the question maybe just just a quick one on.
On the 1000 patients by year end guidance, how how are you getting confident in that number in terms of what the de novo patient growth rate.
Operator: I found it super helpful and that was already three questions, so I'll get back in the queue before Josh comes for me.
But you are seeing sequentially and then quick clarify does that 1000 is that commercial drug or is that include patients.
Operator: Thank you. It's your lucky day.
Operator: We'll take our next question from Paul Matteis from Stiefel. Hey, this is Nathan for Paul.
And expanded access programs.
Operator: Thanks for taking the question. Maybe just a quick one on the 1000 patients by year end guidance. How are you getting confident in that number in terms of like the de novo patient growth rate that you're seeing sequentially, and then quick to clarify, does that 1000 include patients in expanded access programs?
Yes. It includes patients in our.
Expanded access program and also in our.
Ongoing open label study. So we do believe that we're on track to achieve that we're we're roughly at this point over 750 patients.
Operator: Yeah,
Operator: Yeah, it includes patients in our expanded access program and also in our ongoing open label study. So, you know, we do believe that we're, you know, on track to achieve that we're, we're roughly at this point over 750 patients within that universe. And we're very much on track to hit that, you know, over 1000, approximately 1000 patient number by the end of the year. So that's, that's encouraging.
Within that universe, and we're very much on track.
To hit that over thousand approximately thousand.
Patient number by the end of the year. So that's that's encouraging.
Great and then the de Novo patient growth rate just I don't know if you can provide much detail on that sub segment.
Well I mean, Barry can comment as well, but but less when we talk about growth, let's be clear we understand the buckets of growth one is.
Operator: Great, and then the de novo patient growth rate. I don't know if you can provide much detail on that sub-segment.
New patient finding de novo patients being identified and you can look at El Nio, Matt We were getting about a couple of thousand samples per quarter, and we are finding roughly 150 or so patients per quarter and that's been very very steady now for over a year of that program now those are the those aren't necessarily on patra patients. This is just a number that you can look at as a surrogate marker. If you will for patient find it so patient finding is ongoing and as Barry said earlier, it's not just dial back this other.
Operator: Well, I mean, Barry can comment as well, but let's be clear, we understand the buckets of growth, you know, one is new patient finding, and de novo patients being identified. And you can look at Alnylam Act, we're getting about a couple thousand samples per quarter, and we're finding, you know, roughly 150 or so patients per quarter. And that's been very, very steady now for over a year of that program. Now, those aren't necessarily on Patra patients; this is just a number that you can look at as a surrogate marker, if you will, for patient finding. But patient finding is ongoing. And as Barry said earlier, it's not just Alnylam Act, it's other testing programs that are out there.
Its other testing programs that are out there.
Some funded by companies that are not.
So there really is a significant amount of new patient finding happening and by the way. That's just in the US right in Canada as well. So it does it reflect new patient finding around the world, which is also getting better. So thats one source of growth. The second important source of growth is our global expansion.
Operator: You know, some funded by companies, some that are not. So there really is a significant amount of new patient finding happening. And by the way, that's just in the US, right, and Canada as well. So it doesn't reflect new patient finding around the world.
And also in Europe is to see expansion of market access and on a country by country basis, and that's a very important source of growth Barry commented earlier around Japan.
Which we believe by the end of 2020 will be our second largest market.
Operator: Which is also getting better. So that's one source of growth. The second important source of growth is our global expansion. You know, and also in Europe, it's the expansion of market access on a country by country basis. And that's a very important source of growth. Barry commented earlier around Japan, which we believe by the end of 2020 will be our second largest market. And that's going to be an important source of growth in addition to what's going on in the US and what's going on in Europe and the rest of the world. And the final source of growth, which I think it points to the, you know, what we believe to be a remarkable profile of Onpatro, is the evidence generation activities that our medical affairs team and for the longer term, our clinical development team are engaged in to really strengthen the differentiation of Onpatro to help patients understand or physicians understand the best time to use Onpatro for their patients to help highlight, you know, some of the
And that's going to be an important source of growth. In addition to what's going on for us and what's going on in Europe , and the rest of world and the final source of growth, which I think of it points to the.
What we believed to be a remarkable profile of a path ROE is the evidence generation activities that our medical affairs team and for longer term our clinical development team are engaged in to really strengthen the differentiation of on Petro to help patients understand our physicians understand the best time to use on Petro for their patients to help highlight some of the.
Issues that may exist with other therapies that are out there like disease progression, where I'm Patrick can be very helpful. Those type of activities.
We'll have both near term and mid term implications for growth. So let me pause there Barry anything else to add color to conclude great. Thank you.
Operator: I'll end it there.
Operator: Subravo, Thank you.
Operator: Mr. Bravo, thank you guys. Terrific. Next, we'll go to Vincent Chen from Bernstein.
Travel thank you guys.
Terrific.
Next we'll go to Vincent Chen from Bernstein.
Operator: Congratulations on progress and thanks for taking the question. I was wondering if you could provide a little more color on the folks identified in the Alnylam Act with TTR amyloidosis who don't go on Ompatro. What are the reasons for this?
Congratulations on the progress and thanks for taking the question I was wondering if you could provide a little more color on the folks identified and act with TTR amyloidosis dollars going on Paltrow, what are the reasons for this recognizing it's a it's a third party program whether you are certainly very plugged in with the TDR community can you give us a sense for how these patients breakout what portion of mutations associated with new route to the ore mix disease versus a more pure cardium up the phenotype or some ending up in trials et cetera.
Operator: Recognizing it's a third-party program, but you're certainly very plugged in with the TTR community. Could you give us a sense for how these patients break out? What portion of mutations are associated with neuropathy or mixed disease versus a more pure cardiomyopathy phenotype or some ending up in trials, etc.? Or would you expect that many of them would eventually work their way onto Ompatro over time? And as a quick corollary, how does the pace of new star formation look in the second quarter?
Or would you expect that many of them do eventually work their way onto an padro overtime and as a quick corollary, how does the pace of.
Newstar forms look in the second quarter.
Yes. So so maybe just a couple of quick comments, and then I'll hand, it over to Barry.
Operator: Yeah, so maybe just a couple of quick comments, and then I'll hand it over to Barry. You know, we don't have a lot of visibility on specific patients in Alnylam Act, and that's by design. You know, this is a program that's aimed to help physicians diagnose their patients. It's not anything other than that. And obviously, you know, we believe that by improving medical education and patient diagnosis, that if Ompatro is identified as the right choice for treatment for these patients by their physicians, then that will follow. So that has been the philosophy. We just don't have a lot of color other than that in terms of the Alnylam Act. So that's the answer to that one. And then on StarForms, as we said last quarter, you know, we moved away from reporting StarForms as is common in drug launches because of the fact that it's an imprecise measure of
We don't have a lot of visibility on.
Specific patients in Alnylam Act and that's by design.
This is a program that is aimed to help.
Physicians diagnose their patients it's not anything other than that.
And obviously, we believe that by improving medical education, improving patient diagnosis.
That if our patio is identified is the right choice for treatment for these for these patients by their physicians then that will follow so that has been the philosophy. We just don't have a lot of color.
Other than that in terms of Alnylam Act.
So thats the answer to that one and then I'll start forms as we said last quarter, we moved away from reporting star forms as is common in drug launches because of the fact that it's an in precise measure of of patients we have patients in the us and come into our Patra therapy outside of start forms and of course, our farms are use specific measure to begin with so it's not even reflecting true patient growth. The patient number is what you should focus on and obviously revenues very anything else to add what it is.
Operator: We have patients in the U.S. that come into patio therapy outside of Starforms.
Operator: And of course, our forms are a U.S.-specific measure to begin with, so it's not even reflecting true patient growth. The patient numbers are what you should focus on, and obviously revenues. Barry, anything else to add to what I just said?
Operator: I think you covered it well. Back to the Alnylam Act. Again, just to reiterate, Alnylam Act is a free, third-party genetic test that we and other companies offer other tests for the benefit of patients. And just to give you some color, Vincent, what we often see is that a patient will come in after a multi-year journey, finally be diagnosed with HHH hemodialysis, and through genetic counseling, identify that they have this disease in their siblings, children, and others. And those people often then will visit a physician for a genetic test. So the Alnylam Act really eases the burden for the benefit of patients to get these genetic tests. As John said, it's an arm's length relationship because it's there for the benefit of patients. Now, some patients do not yet have penetrance for the disease, but we believe that by raising awareness, remember, this is not about a portion of the pie; it's growing your overall pie, that will continue to benefit patients by raising awareness and speeding up diagnosis.
You covered it well just back to on IMAX again, just to reiterate I'll now Matt is a free third party genetic test that we and other companies other companies offer other tests for the benefit of patients.
And just to give you some color Vincent what we often see is that.
Patients will come in after a multi year journey filing but be diagnosed with HKG generally doses and through genetic counseling identifies that they have this disease to their siblings children and others and those people often then we'll we'll visit a physician for genetic tests. So all myeloma really eases the burden for the benefit of patients to get these genetic test is as John said.
It's a it's an arm's length relationship because we're there for the benefit of patients now some patients do not yet have penetrance of disease, but we believe that by raising awareness remember this is not about a portion of the pie is growing their overall pie that will continue to benefit patients by raising awareness and speeds diagnosis.
I see thank you very much.
Operator: Thank you very much. Our next question today is from Ted Tentoff of Kuiper Daffrey.
Our next question today is from Ted Tenthoff from Piper Jaffray.
Operator: Great, thank you very much, and congratulations on the progress. Thank you. Yeah, a really, really impressive global launch. And just a comment, I love that you guys are breaking it out globally. It really gives us a sense of where the patients are coming from and where the growth is coming from. So, thank you for that. Kind of looking at VitruSan and really considering sort of how this market could evolve, you know, tell us a little bit more about where you think sort of IV versus sub-Q might be used and maybe even if there would be induction versus maintenance or just give us a little bit more of a sense of sort of how you see all of that playing out.
Great. Thank you very much and congrats on the progress.
Thanks, Dan.
Really really impressive global launch just a comment I love that you guys are breaking it out globally really gives us a sense, where the patients are coming from and the growth is coming from so thank you for that.
Looking at pictures, and really considering sort of how this market could evolve.
Ill tell us a little bit more about where we think sort of the versus yours and maybe even if you will.
Induction versus maintenance or just give us a little bit more of a sense of sort of how you see all of that playing out. Thank you.
Operator: Yeah, thanks, Ted. And thanks for your thanks for your comments earlier.
Yes, Thanks, Ted and thanks for your thanks for your comments earlier.
Operator: I mean, we're extremely excited about Boutriseran. It's a once-quarterly, you know, low dose, low volume, subcutaneous injection that, you know, we think is an exciting, you know, expansion of the overall ATTR opportunity. I mean, taking a step back, when you think about this market, you think about hereditary ATTR, polyneuropathy, where we are today, and then in the future, expanding into cardiomyopathy, if our studies are successful. And then you think about the wild type setting again, with studies like Apollo B and Helios B, assuming those studies are successful. We've got a remarkable opportunity for the overall franchise for many, many years to come. And, you know, I think, without getting Hedi or Heidi in terms of numbers.
I mean, we're extremely excited about Patrice around it's a it's a once quarterly.
Low dose low volume subcutaneous injection that.
We think is exciting.
Expansion of the overall HCR opportunity I mean, taking a step back.
When you think about the this market. If you think about hereditary TTR polyneuropathy, where we are today in that in the future expanding into cardium off of the of our studies are successful and then you think about the wild type setting again with studies like Apollo be at Healios be assuming those studies are successful we've got a remarkable opportunity for the overall franchise.
For many many years to come and.
I think.
Without without getting.
How many or how do you see in terms of numbers I mean, this really is a multi billion type of market opportunity, where alnylam is poised to be a significant leader. So patrice ran really positions us with an with a product offering that.
Operator: I mean, this really is a multi-billion-dollar market opportunity where Alnylam is poised to be a significant leader. So Boutrisran really positions us with a product offering that, you know, really provides a great option for patients. You know, Helios A will bring medicine to patients quickly, rapidly. That study is up and going and rolling. We expect that to read out in the 21-22 time period, and that it will be important for patients to get access to a sub-Q alternative like Boutrisran. And then Helios B, which will start up very shortly by the end of the year, that really addresses...
Really provides a great option for patients.
With Healios AE will break this into patients.
Critically rapidly that study is up and going and rolling we expect that to read out of the 20 122 time period that will be important for patients to get access to Subcu alternative.
Like like which we trend and then healios be which will start out very shortly by the end of the year that really addresses the larger commercial opportunity in the wild type and hereditary Cardium, obviously say a very very significant opportunity with a once quarterly subcutaneous option that we think is extremely competitive and we've done studies to show that is even preferred over an oral oral agent given once a day or even.
Operator: We have a very, very significant opportunity with a once-quarterly subcutaneous option that we think is extremely competitive. And we've done studies to show that it's even preferred over an oral agent given once a day or, you know, even less excitingly, twice a day. So, these are really opportunities for market growth and expansion for Alnylam that are not that far away at all and very, very exciting to look forward to.
Less less Excitingly twice a day. So these are these are really opportunities for market growth and expansion for alnylam that is not that far away at all and very very excited to look forward to so Barry anything else to add to that I think you covered it well I guess the only.
Operator: I think you covered it well. I guess there are only two things.
Operator: One interesting analog to look at is how the MS market has developed over the last 30 years. And if you think 30 years ago to today and project out the ATTRM leidosis market over the next 10 to 15 years, we can see a dynamic where more prescribers are getting interested, diagnosis gets much earlier in the disease, and patients benefit more from an earlier diagnosis. So, just in addition to what John mentioned, I see those same dynamics playing out with ATTRM leidosis.
Two things one is an interesting analog to look at is how the mass market developed over the last 30 years and if you think 30 years ago today and project out the 80 generally dose mark over the next 10 to 15 years, we can see a car a dynamic where.
More prescribers are getting interested diagnosis.
Gets much earlier in the disease and and patients benefit greater by an earlier diagnosis. So you. Just in addition to John mentioned I see those same dynamics playing out are they determine the doses.
Operator: Great, I appreciate all the color, and you're building a great foundation on them, Patra, so thanks so much.
Great I appreciate all the color and suburban liquid from this enrollment process for consumers.
Operator: Thank you, Taz.
Thank you Ted.
Operator: And we'll go next to David Lebowitz from Morgan Stanley. Thank you very much for taking my question. Could you characterize the effort it takes to transition patients that are diagnosed in the Alnylam Act program to actually being patients on drugs? And noticing that there are certainly more patients that are from the cardio end, I guess, given that the drugs approved for polyneuropathy are coming online for the drug. What could be driving the fact that so many cardio patients are coming on?
And we'll go next to David Liebowitz from Morgan Stanley .
Thank you very much for taking my question.
Could you characterize the effort it takes to transition patients that are diagnosed and the alnylam akt program to actually being patients on drug.
And then noticing that there is certainly more patients that are from the cardio and I guess.
Given that the drugs approved for Polyneuropathy coming online for the drug.
What would be driving the fact that so many cardio patients are coming on.
Operator: Sure, let's, Barry, you want to handle it?
Sure, let us very well to handle.
Operator: More broadly, there are a number of things we're doing to increase awareness and diagnosis. Hereditary T-tremor meiosis is unfortunately a disease where patients can bump into cardiologists, neurologists, other specialties who misdiagnose the disease. And that dynamic continues until awareness is raised.
Yes, I mean, I guess more broadly.
And just again to say that there is a number of things we're doing to increase.
Awareness and diagnosis hereditary TTR amyloidosis is unfortunately disease, where patients can bump into.
Cardiologists neurologist other specialties, who miss or Miss diagnose the disease and that that dynamic continued until awareness is raised.
Operator: Now specifically in the cardiology front, if a patient presents... With cardiovascular symptoms, there are tools that cardiologists have and are using now more and more echo technetium scanning that helps point to amyloidosis and specifically TTR amyloidosis, which is why we see the cardiology community so interested. And then, of course, there are many, many wild-type patients, the segment that we're not yet penetrating commercial We will in the future, assuming positive data, and because there are so many wild-type patients, cardiologists are becoming more and more aware. Now, importantly, we're also seeing on the neurology side more awareness of TTR amyloidosis, and hereditary treatment. They are looking for the disease using the tools they have, so we see that all as positive signs of improved diagnosis and speedier diagnosis. Right. And Akshay? Yeah,
Now specifically the cardiology front of a patient presents.
With cardiovascular symptoms there are tools the cardiologist have and are using now more and more eco technetium scanning that helps point too.
And we do have some specifically T terminally doses, which is why we see the cardiology community. So interested and then of course there are many many wild type patients. The segment that were not yet penetrating commercially we will in the future assuming positive data and because there's so many wild type patients cardiology coming more and more aware now importantly, we're also seeing on the neurology side more awareness of TTR amyloidosis hereditary team and they are looking for the disease using the tools. They have so we see that all is positive signs of improved diagnosis and speedier diagnosis vary and contract. Yes, I mean, just to build on what Barry was saying if we look at the U.S. landscape in many senses feeble into two items the commonest mutation.
Operator: Yeah, I mean, just to build on what Barry was saying, if we look at the U.S. landscape, in many senses, B.1.2.2i is the commonest mutation, but the other important thing to bear in mind is that there's increasing awareness that a very significant proportion of those patients have neuropathy. What Barry has seen, and I've seen, when I've spoken to doctors, is cardiologists are increasingly looking increasingly heavy for neuro They're collaborating with their neurologists in multifunctional teams to fully characterize the multidisciplinary nature of the disease and, as appropriate, if they have neuropathy, then prescribe a relevant drug like Onpatro.
But the other important thing to bear in mind is that there is increasing awareness that a very significant proportion of those patients have neuropathy.
Well Barry is seen I've seen and I've spoken to Delta's is cardiologist looking okay.
You can see full neuropathy that collaborating with and neurologists than a multi functional teams to fully characterize the most is letting nature of the disease and as appropriate if they have neuropathy than to prescribe.
Rather the drug like on Patrick So.
Operator: So, you know, Barry's absolutely right. It's a journey. Education and awareness are increasing. And it's great that patients who have B.1.2.2i and other mutations are getting more fully characterized so physicians and patients understand the full burden of disease, and as I said, where appropriately found neuropathy than certainly on patro is an important test.
You know Barry that's a right. It's a journey the education awareness is increasing and it's great that patients who have gone to July .
And other mutations are getting more fully characterize so physicians and patients on this on the full burden of disease and as I said were appropriate time neurons Stephen setting on contract isn't important choice for them.
Operator: Does that answer your question?
Does that answer your question.
Operator: Thank you very much. I appreciate it.
Thank you very much I appreciate it.
Operator: Thank you. Okay, so go ahead, operator, Kim.
Great. Thank you.
Okay. So.
No go ahead operator, Kevin.
Operator: That's all the time we have.
That's all the time, we have for questions I'll turn it back to the company for closing remarks.
Operator: Great. Well, thanks, everyone, for joining us on the call. We're obviously very pleased with the R&D and commercial progress that we've been making. We are really excited about the company that we're building, and the impact we're making on patients' lives. So with that, I look forward to updating you on our continued progress in the coming weeks and months. Have a great rest of the day, everybody. Bye-bye.
Great well, thanks, everyone for joining us on the call. We're obviously very pleased with the R&D and commercial progress that we've been making we are really excited about the company that we're building the impact we're making on patients lives. So with that I look forward to updating you on our continued progress in the coming weeks and months have a great rest today everybody bye bye.
Operator: And that does conclude our conference today. Thank you for your participation. You may now disconnect. Copyright 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent.
And that does conclude our conference today. Thank you for your participation you may now disconnect.