Cytokinetics released several new analyses of the SEQUOIA-HCM Phase III trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The company also presented retrospective real-world data in non-obstructive HCM, offering a broader picture of disease burden and potential opportunities for treatment innovation. The findings were presented at the European Society of Cardiology Heart Failure 2025 Congress.

The SEQUOIA-HCM trial is evaluating aficamten, a next-generation cardiac myosin inhibitor, in patients with oHCM. The newly shared data focused on how patients responded based on their baseline symptom severity and their geographic region. Patients were divided into two subgroups: those with mild symptoms, defined as New York Heart Association (NYHA) Class II and a high Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS ≥ 80), and those with moderate to severe symptoms, defined as NYHA Class II/III/IV with a KCCQ-CSS below 80.

After 24 weeks of treatment, both groups demonstrated meaningful improvements in exercise capacity. Patients with mild symptoms gained about 1.6 mL/kg/min in peak oxygen uptake (pVO₂), while those with more severe symptoms gained 1.8 mL/kg/min. Improvements in quality of life were more pronounced in the moderate to severe subgroup, though more than half of the patients with mild symptoms became asymptomatic by the end of the study. Over 50 percent of participants in both groups improved by at least one NYHA functional class.

The analyses also explored differences across regions, including Europe, North America, and China. Patients in China generally presented with lower body mass index, fewer comorbidities, and milder symptoms compared to those in other regions. Despite these baseline differences, aficamten demonstrated consistent efficacy across all geographies. Improvements were observed in exercise performance, reductions in left ventricular outflow tract gradients, and favorable changes in biomarkers such as NT-proBNP and high-sensitivity troponin I. Safety findings were also consistent, with no unexpected adverse events reported.

In addition, real-world data from patients with non-obstructive HCM between 2013 and 2021 were analyzed. The results revealed that patients aged 75 or older had the highest all-cause mortality rates, reaching nearly 17 percent. Women with non-obstructive HCM experienced higher risks of cardiovascular events, including stroke and hospitalization, compared with men. These findings highlight the unmet medical need in non-obstructive HCM, a population with fewer therapeutic options than patients with obstructive disease. Early signals from ongoing aficamten studies in non-obstructive HCM suggest potential benefits, though variability is greater and further investigation will be required.

Why it matters

Hypertrophic cardiomyopathy is one of the most common inherited heart diseases, yet options for patients with the non-obstructive form remain limited. The SEQUOIA-HCM analyses show that aficamten can provide clinical improvements across a broad spectrum of patients with obstructive disease, including those with milder symptoms who are often left to “wait and watch” under current treatment paradigms.

The consistency of results across different global regions is also encouraging, as regulators often require evidence that therapies work in diverse populations. This could smooth the path toward broader approvals and access. At the same time, the disparities observed in non-obstructive HCM — particularly for older adults and women — underscore the importance of targeted strategies to close treatment gaps.