Roche, AbbVie say trial of Venclexta in patients with myelodysplastic syndromes falls short

Roche and AbbVie's Venclexta failed to meet its primary endpoint of overall survival in a Phase 3 trial for previously untreated patients with higher-risk myelodysplastic syndromes (MDS), marking another setback for the blockbuster blood cancer treatment; this is the second recent trial failure, following disappointing results in multiple myeloma, despite Venclexta achieving $2.6 billion in sales last year.

Analysis

Roche and AbbVie's Venclexta has encountered another significant clinical setback, failing to meet its primary endpoint of overall survival in a Phase 3 trial targeting previously untreated higher-risk myelodysplastic syndromes (MDS). The study, involving approximately 500 patients, compared Venclexta combined with azacitidine against placebo plus azacitidine. This failure curtails a potential label expansion for Venclexta, which is currently approved for chronic lymphocytic leukemia (since 2016) and acute myeloid leukemia (AML, fully approved 2020). This marks the second recent trial disappointment for the drug, following the 2023 Canova study where Venclexta, in combination with dexamethasone, did not achieve statistically significant progression-free survival improvement in relapsed/refractory multiple myeloma patients compared to Bristol Myers Squibb’s Pomalyst plus dexamethasone. Historically, Venclexta faced a major setback in 2019 due to increased deaths in its arm of a Phase 3 multiple myeloma trial (Bellini), leading to a clinical hold, which was later lifted; the Bellini trial ultimately showed improved progression-free survival but also resulted in increased mortality in the overall patient population compared to the control arm. Despite these challenges in expanding its indications, Venclexta, a BCL-2 inhibitor, achieved blockbuster status in 2020 and recorded sales of $2.6 billion last year, an increase of 13% year-over-year, underscoring its commercial strength in approved uses. The current MDS trial failure, however, carries a moderately negative sentiment, particularly for AbbVie (ABBV), and is expected to have a moderate market impact based on the provided signals.

Key Decisions for Investors

• Investors should scrutinize the full data presentation from the MDS trial, expected at an upcoming medical meeting, for any subgroup analyses or detailed findings that might offer nuanced insights into Venclexta's potential or lack thereof in this patient population.
• Given the repeated Phase 3 failures in new indications (MDS and multiple myeloma), AbbVie investors should re-evaluate the long-term growth trajectory of Venclexta, as its expansion potential beyond current approvals appears increasingly constrained.
• While the pipeline setbacks for Venclexta are concerning, investors should also weigh its existing $2.6 billion annual sales and ongoing 13% year-over-year growth in its established indications when assessing the overall impact on AbbVie's revenue and profitability.