Cytokinetics' aficamten hits dual Phase 3 endpoints in nHCM

Cytokinetics has reported positive topline results from ACACIA-HCM, its pivotal Phase 3 trial of aficamten (MYQORZO) in symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM), with the study meeting both dual primary endpoints at Week 36.

The trial — a 516-participant, randomised, double-blind, placebo-controlled study — measured changes in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and peak oxygen uptake (pVO₂). Aficamten produced a least-squares mean improvement of 11.4 points on the KCCQ-CSS versus 8.4 points for placebo (difference: 3.0 points; p=0.021), and a pVO₂ gain of 0.64 mL/kg/min compared with a marginal decline of 0.03 mL/kg/min on placebo (difference: 0.67 mL/kg/min; p=0.003).

Key secondary endpoints — including NYHA functional class improvement, a composite cardiopulmonary exercise score, and NT-proBNP reduction — also reached statistical significance (p<0.001).

Safety and tolerability

No new safety signals were identified. Completion of planned dosing was broadly comparable between arms (88.4% aficamten versus 90.3% placebo). Left ventricular ejection fraction below 50% occurred in 10% of aficamten-treated participants versus 1% on placebo; two participants on aficamten experienced a serious adverse event of heart failure associated with reduced LVEF. Treatment interruptions due to LVEF below 40% occurred in 3% of the aficamten group. These findings are consistent with the known mechanism of cardiac myosin inhibition and the established REMS programme that governs MYQORZO's use in obstructive HCM.

Fady I. Malik, Cytokinetics' Executive Vice President of Research & Development, said the results represent "the first clinical trial to demonstrate statistically significant improvements in exercise capacity and symptom burden in patients with non-obstructive HCM," adding that the company intends to present full data at an upcoming medical meeting and engage with the FDA and other regulators.

Market context and regulatory path

The significance of ACACIA-HCM lies in an unmet need with no currently approved pharmacological options. Non-obstructive HCM accounts for roughly half of all HCM cases in the United States, a population estimated at more than 300,000 diagnosed patients — with a further 400,000 to 800,000 estimated to remain undiagnosed. A positive regulatory submission would substantially expand aficamten's addressable market beyond the obstructive indication for which MYQORZO already holds approval in the US, EU and China.

Bristol Myers Squibb's mavacamten (Camzyos), the first approved cardiac myosin inhibitor, is currently indicated only for obstructive HCM, leaving the non-obstructive segment open. Cytokinetics will need to navigate the FDA's expectations around the clinical meaningfulness of the KCCQ and pVO₂ endpoints — both patient-relevant measures that regulators have accepted in HCM submissions previously — as well as the heart failure risk flagged in the safety data. The company has prior experience managing the REMS framework, which should facilitate discussions on the labelling approach for nHCM.

Full data presentation and regulatory agency interactions will be the near-term catalysts for investors tracking this programme. Cytokinetics is also developing omecamtiv mecarbil in heart failure with severely reduced ejection fraction and ulacamten for heart failure with preserved ejection fraction, giving the company a broader cardiac muscle biology pipeline beyond HCM.