Amicus Therapeutics Publishes Positive Post-Hoc Analysis of Cipaglucosidase Alfa-Atga + Miglustat in Late-Onset Pompe Disease

Amicus Therapeutics (FOLD) announced positive findings from a post-hoc analysis of the PROPEL study, published in Muscle and Nerve, evaluating cipaglucosidase alfa-atga combined with miglustat (cipa+mig) in adults with late-onset Pompe disease (LOPD). The analysis showed that patients transitioning from alglucosidase alfa to cipa+mig experienced significant improvements or stability in motor function and fatigue, while those remaining on the original treatment generally worsened; specifically, improvements were seen in walking distance and muscle testing. These results support the potential benefits of switching to cipa+mig for LOPD patients, though the original PROPEL study did not achieve statistical significance for its primary endpoint.

Analysis

Amicus Therapeutics (Nasdaq: FOLD) has reported positive outcomes from a post-hoc analysis of its PROPEL study, published in *Muscle and Nerve*, for cipaglucosidase alfa-atga combined with miglustat (Pombiliti + Opfolda) in adults with late-onset Pompe disease (LOPD). The analysis indicated that ERT-experienced patients (n=65) switching from alglucosidase alfa to cipa+mig demonstrated improvements or stability across multiple domains, including a 17-meter (95% CI, 0.2, 33) farther 6-minute walk distance and a 3.5% (95% CI, 1.0, 6.0) improvement in forced vital capacity (FVC) compared to the comparator group after 52 weeks. Improvements were also noted in patient-reported fatigue and muscle strength. This contrasts with patients who remained on alglucosidase alfa, who generally experienced worsening or stable symptoms. The PROPEL study maintained a high completion rate of over 95% (117 out of 123 patients). However, it's crucial to note that the original PROPEL study did not achieve statistical significance for its primary endpoint of superiority in 6MWD in the overall population, and these positive findings stem from a post-hoc analysis, which may temper enthusiasm regarding their robustness. Institutional activity shows mixed sentiment: Point72 Asset Management and Millennium Management initiated significant new positions in Q1 2025, adding 2.99M and 2.90M shares respectively, while Fiera Capital Corp exited its entire 3.04M share position. Other notable decreases include Perceptive Advisors LLC (-2.78M shares) and Avoro Capital Advisors LLC (-2.68M shares). Insider activity includes one sale by CEO Bradley L Campbell of 400 shares in the past six months. Analyst coverage includes a "Buy" rating from UBS issued on May 2, 2025. These findings reinforce the potential for Pombiliti + Opfolda as a treatment option for LOPD patients not improving on current enzyme replacement therapy.

Key Decisions for Investors

• Investors should consider the positive post-hoc clinical data for Pombiliti + Opfolda, which suggests a potential therapeutic benefit for a subset of LOPD patients and could support market penetration, but weigh this against the original PROPEL study's failure to meet its primary endpoint.
• The mixed institutional holdings, with significant new entries and complete exits, alongside a minor insider sale, warrant careful evaluation of conviction levels among large shareholders and management.
• Monitor upcoming regulatory feedback, real-world adoption rates of Pombiliti + Opfolda, and any further clinical trial data or publications to assess the long-term commercial viability and competitive positioning of Amicus Therapeutics in the LOPD market.