Cytokinetics' Phase III Aficamten Data Challenges BMS in Cardiomyopathy

Cytokinetics recently revealed promising results from its Phase III SEQUOIA-HCM clinical trial. The study showed that aficamten, an investigational cardiac myosin inhibitor, significantly boosted exercise capacity in individuals with obstructive hypertrophic cardiomyopathy (HCM).

At the 24-week mark, patients taking aficamten experienced a 1.8-mL/kg/min increase in peak oxygen uptake, a critical measure of exercise capacity. In contrast, those on a placebo saw no change. This improvement was statistically significant and consistent across various patient demographics, including age, sex, and concurrent use of beta-blockers.

Additionally, aficamten met key secondary endpoints by significantly reducing symptom severity compared to placebo. This was measured using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. At the same 24-week point, the drug also notably decreased levels of NT-proBNP, a biomarker indicating cardiac wall stress.

Safety evaluations from SEQUOIA-HCM indicated that aficamten was well-tolerated, with an adverse event profile comparable to the placebo group. Importantly, there were no reports of worsening heart failure or treatment discontinuation due to side effects. These findings were concurrently published in The New England Journal of Medicine.

Dr. Fady Malik, Executive Vice President of R&D at Cytokinetics, noted that aficamten is associated with rapid, sustained improvements in exercise capacity, symptoms, cardiac function, and biomarkers in obstructive HCM patients. These results strongly support the potential for aficamten's approval. Cytokinetics plans to submit regulatory filings in the U.S. and Europe by the end of the year.

This positive outcome moves Cytokinetics closer to its first drug approval, marking a significant turnaround for the company. Earlier this year, Cytokinetics faced setbacks when the FDA declined to approve omecamtiv mecarbil, another cardiac myosin activator aimed at treating heart failure. The FDA found the Phase III data insufficient and requested another trial. Cytokinetics decided not to pursue further trials for the drug and later discontinued development of reldesemtiv, a candidate for amyotrophic lateral sclerosis, after unsatisfactory Phase III results.

If aficamten gets approved, it will join the market alongside Bristol Myers Squibb's Camzyos (mavacamten), an oral medication approved in April 2022 for obstructive HCM patients classified as New York Heart Association Class II to III. Notably, Camzyos carries a boxed warning for heart failure due to systolic dysfunction.

These new data from the SEQUOIA-HCM trial underscore the potential of aficamten as a transformative treatment for patients with obstructive hypertrophic cardiomyopathy.