Cytokinetics Shares New SEQUOIA-HCM Data at HFSA Meeting

Cytokinetics, Inc. has unveiled new findings from SEQUOIA-HCM, a pivotal Phase 3 trial examining aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The data were presented virtually at the Heart Failure Society of America (HFSA) Annual Scientific Meeting by Dr. Martin Maron and published concurrently in the Journal of the American College of Cardiology.

The responder analyses of SEQUOIA-HCM evaluated aficamten against a placebo, both in conjunction with standard care. Key integrated clinical assessments were scrutinized after 24 weeks of treatment. These assessments included hemodynamic response, symptom relief, enhanced exercise capacity, and cardiac biomarker response.

The results were notable: 68% of aficamten-treated patients achieved complete hemodynamic response compared to just 7% with placebo. Additionally, 71% of those on aficamten experienced symptom relief versus 42% on placebo. Enhanced exercise capacity was observed in 46.5% of aficamten patients compared to 24% on placebo, and a substantial cardiac biomarker response was noted in 84% of aficamten patients against 8% with placebo. The statistical significance of these outcomes was marked, with all comparisons yielding p-values less than 0.002 relative to placebo.

Aficamten demonstrated a compelling overall efficacy, with 97% of patients achieving at least one clinically relevant outcome. Furthermore, 62% of patients achieved at least three outcomes, and 23% achieved all four. The number needed to treat (NNT) for each of the four outcomes was fewer than five patients, suggesting high efficacy.

Additional analyses showed that 42% of aficamten patients enhanced their functional capacity compared to 14% on placebo, resulting in a 29% difference (95% CI: 18.8 - 38.6, p<0.001) and an NNT of three. Moreover, among those eligible for septal reduction therapy at baseline, 88% of aficamten-treated patients were no longer eligible at 24 weeks (p=0.002).

Dr. Stephen Heitner, Vice President and Head of Clinical Research at Cytokinetics, highlighted the significance of these findings. "In these prespecified analyses of SEQUOIA-HCM, the addition of aficamten to standard care was associated with improvements in four key clinical markers used by cardiologists for HCM patient management. This data augments the primary results from SEQUOIA-HCM, further underscoring aficamten's potential as a next-in-class cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy."

Aficamten, a selective small molecule cardiac myosin inhibitor, has shown promise in reducing myocardial hypercontractility associated with HCM. It works by binding to a specific allosteric site on cardiac myosin, preventing it from entering a force-producing state. This mechanism aids in reducing the myocardial contractility that characterizes HCM.

The development program for aficamten is extensive, focusing on improving exercise capacity and symptom relief in HCM patients, as well as assessing long-term cardiac structural and functional impacts. The drug has received Breakthrough Therapy Designation from the U.S. FDA and the National Medical Products Administration (NMPA) in China for treating symptomatic obstructive HCM.

Cytokinetics is also exploring aficamten in other clinical trials, such as MAPLE-HCM, which compares aficamten monotherapy to metoprolol in obstructive HCM patients; ACACIA-HCM, which examines aficamten in non-obstructive HCM patients; CEDAR-HCM, focusing on pediatric patients with obstructive HCM; and FOREST-HCM, an open-label extension study.

The company remains committed to advancing treatments for debilitating cardiovascular diseases, leveraging its expertise in muscle biology to bring innovative therapies to market.