Cytokinetics has announced that additional analyses synthesizing data from SEQUOIA-HCM, the pivotal phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).
The data were presented by Martin Maron (Lahey Hospital and Medical Center, Burlington, USA) as part of the Heart Failure Society of America (HFSA) annual scientific meeting. The meeting had been due to take place 27–30 September in Atlanta, USA, but had been cancelled due to Hurricane Helene. Late-breaking studies that had been due to be presented in-person at HFSA 2024 were live-streamed online. The presentation was also simultaneously published in the Journal of the American College of Cardiology.
In these responder analyses of data from SEQUOIA-HCM, key integrated clinical assessments were analysed following 24 weeks of treatment with aficamten or placebo (in addition to standard of care in both cases) in the study population (n=282): 1) complete haemodynamic response (resting and Valsalva left ventricular outflow tract gradient [LVOT-G] <30 mmHg and <50 mmHg, respectively), 2) relief of symptoms (≥1 change in New York Heart Association [NYHA] Functional Class and/or ≥10-point increase in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CCS]), 3) enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake [pVO2]), and 4) cardiac biomarker response (≥50% reduction in NT-proBNP).
Comparing patients treated with aficamten to placebo, 68% vs. 7% demonstrated a complete haemodynamic response, 71% vs. 42% experienced relief of limiting symptoms, 46.5% vs. 24% showed enhanced exercise capacity and 84% vs. 8% demonstrated a substantial response in cardiac biomarkers (for all p<0.002 compared to placebo).
Overall, 97% of patients treated with aficamten achieved one or more clinically relevant outcomes, 62% achieved at least three outcomes and 23% achieved all four outcomes. For each of the four outcomes assessed in these analyses, the number needed to treat (NNT) was fewer than five patients.
In a responder analysis of functional capacity (defined as pVO2 ≥1.5mL/kg/min and ≥1 improvement in NYHA class, or pVO2 ≥3.0 mL/kg/min2 and no worsening in NYHA class), 42% of patients on aficamten and 14% of patients on placebo were responders, for a difference vs. placebo of 29% (95% CI: 18.8 – 38.6, p<0.001) and an NNT of 3.
Additionally, among patients treated with aficamten who were eligible for septal reduction therapy at baseline (n=32), 88% were no longer eligible at 24 weeks (p=0.002 compared to placebo).
“In these prespecified analyses of SEQUOIA-HCM the addition of aficamten to standard of care was associated with important improvements in four key clinical markers used by cardiologists to inform HCM patient management strategies and prognosis. Included in these assessments are a complete haemodynamic response which was demonstrated in two-thirds of the patients in SEQUOIA-HCM,” said Stephen Heitner, vice president, head of clinical research, Cytokinetics. “These data elaborate on the primary results from SEQUOIA-HCM and further inform the relevance to clinical practice of aficamten as a next-in-class cardiac myosin inhibitor for adult patients with obstructive HCM.”
