Cytokinetics Halts ALS Drug Trial and Faces FDA Rejection for Heart Failure Treatment
核心洞察
Cytokinetics (搜索) stopped the Phase 3 COURAGE-ALS (搜索) trial of resedemtiv (搜索) for amyotrophic lateral sclerosis (搜索) (ALS) after a futility analysis showed no benefit over placebo.
The FDA rejected Cytokinetics (搜索)' omecamtiv mecarbil for heart failure (搜索), citing insufficient efficacy data, increasing the likelihood that the company will shelve the drug.
Cytokinetics (搜索) is now focusing on aficamten, a cardiac myosin (搜索) inhibitor in Phase 3 development for hypertrophic cardiomyopathy (搜索) (HCM (搜索)), with results expected later in 2023.
Cytokinetics (搜索) has faced significant setbacks with the termination of its Phase 3 trial for resedemtiv (搜索) in amyotrophic lateral sclerosis (搜索) (ALS (搜索)) and the FDA's rejection of omecamtiv mecarbil for heart failure (搜索). These developments have shifted the company's focus towards aficamten, a drug targeting hypertrophic cardiomyopathy (搜索) (HCM (搜索)).
Resedemtiv Trial Halted
The Phase 3 COURAGE-ALS (搜索) trial, involving 555 patients, assessed the efficacy of resedemtiv (搜索) in treating ALS. However, a futility analysis revealed that resedemtiv did not demonstrate a statistically significant improvement over placebo in the primary endpoint, measured by the change from baseline to 24 weeks on the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary endpoints also showed no benefit. Consequently, Cytokinetics (搜索) has decided to abandon the trial and its open-label extension study, COURAGE-ALS-OLE.
Robert Blum, CEO of Cytokinetics (搜索), expressed disappointment with the outcome and indicated that the company would assess the next steps for its neuromuscular development programs. This decision follows concerns raised after the Phase 2 FORTITUDE-ALS (搜索) trial, where resedemtiv (搜索) failed to show a statistically significant improvement over the control.
FDA Rejection of Omecamtiv Mecarbil
Cytokinetics (搜索) also received a complete response letter from the FDA rejecting its marketing application for omecamtiv mecarbil, a cardiac myosin (搜索) activator intended for heart failure (搜索) treatment. The FDA's decision aligns with the recommendation of its advisory committee, which concluded that the drug's efficacy did not outweigh its potential side effects, including cardiotoxicity and myocardial ischaemia.
The application was primarily based on the GALACTIC-HF study, which showed an 8% reduction in cardiovascular death or heart failure (搜索) events compared to placebo. However, the FDA deemed this evidence "not sufficiently persuasive." Additionally, the METEORIC-HF trial failed to demonstrate improved exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF) treated with omecamtiv mecarbil compared to placebo.
Focus on Aficamten for HCM
With the setbacks for resedemtiv (搜索) and omecamtiv mecarbil, Cytokinetics (搜索) is now prioritizing the development of aficamten, a cardiac myosin (搜索) inhibitor in Phase 3 clinical trials for symptomatic hypertrophic cardiomyopathy (搜索) (HCM (搜索)). The SEQUOIA-HCM pivotal trial is expected to generate results later in 2023, with two additional studies planned to commence before the end of the year.
Aficamten is seen as a potential blockbuster in HCM (搜索), a condition characterized by the thickening of the heart muscle, which can obstruct blood flow and lead to symptoms such as chest pain and palpitations. In the REDWOOD-HCM trial, aficamten demonstrated statistically significant improvements over placebo, with blood flow reaching the normal range in 13 out of 14 patients with obstructive HCM after 10 weeks of treatment at the highest dose.
However, aficamten faces competition from Bristol-Myers Squibb (搜索)'s Camzyos (mavacamten), which is already approved for obstructive HCM (搜索). The annual cost of Camzyos is approximately $90,000 before reductions, posing a challenge to its widespread adoption in a market currently managed by cheaper generic treatments like disopyramide.