Cytokinetics presents additional ACACIA-HCM data on aficamten in nHCM
Cytokinetics has presented three additional analyses from its ACACIA-HCM Phase 3 trial at the Heart Failure Society of America Annual Scientific Meeting 2026 in Phoenix, adding granularity to earlier topline results for aficamten in non-obstructive hypertrophic cardiomyopathy (nHCM).
The presentations covered a novel composite exercise score, a global efficacy responder analysis, and a detailed breakdown of dose titration and safety. Together, the data are intended to support the company's plan to file a supplemental New Drug Application (sNDA) with the FDA in the fourth quarter of 2026.
Exercise performance and clinical response
The first late-breaking presentation used the 2026 Boston Exercise Aggregate Physiologic Response Score (BEAP-RS), a composite metric spanning five exercise and recovery domains. At 36 weeks, patients treated with aficamten showed a statistically significant improvement in BEAP-RS versus placebo (p less than 0.001), with gains across every individual domain. Improvements in the composite score also correlated significantly with better scores on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and New York Heart Association functional class, as well as reductions in the cardiac biomarker NT-proBNP, suggesting the exercise gains are tracking alongside broader functional and biochemical improvements.
The global efficacy responder analysis, published in Circulation in August 2026, assessed clinical response across five domains at 36 weeks. Aficamten produced statistically significant improvements in four of the five: relief of limiting symptoms, reduction in left atrial volume index, increase in septal e' velocity, and a 50% or greater reduction in NT-proBNP. On the fifth domain, at least a 0.5 mL/kg/min increase in peak VO2 was observed in 45% of aficamten patients versus 37% on placebo, though this difference did not reach statistical significance. Overall, 53% of patients on aficamten met the threshold for response in three or more domains, against 13% on placebo (p less than 0.001).
Dose titration and safety signals
The dose titration analysis showed that by the end of the titration period, approximately 81% of patients had reached the 15 mg or 20 mg dose. Plasma concentrations and reductions in left ventricular ejection fraction (LVEF) tracked dose proportionally, with LVEF stabilising from week 8 onward. LVEF falling below 50% occurred in 10.5% of aficamten patients versus 0.8% on placebo. In total, 12 patients on aficamten (4.7%) experienced serious adverse events of heart failure, compared with three patients on placebo (1.2%). All heart failure events occurred during titration or before week 12, often following precipitating events such as rapid atrial fibrillation or infection, and resolved with standard medical management. Stephen Heitner, Cytokinetics' Chief Medical Officer, said the data "reinforce our confidence in the safety and treatment effect of aficamten in nHCM."
Market context and competitive landscape
The nHCM space has attracted significant attention since mavacamten, marketed as Camzyos by Bristol Myers Squibb, established proof of concept for cardiac myosin inhibition in obstructive HCM. Aficamten is already approved in the US, EU, UK and China for obstructive HCM under the brand name MYQORZO, and a successful sNDA for nHCM would meaningfully expand the addressable market. Approximately half of all HCM patients have the non-obstructive form, representing a population that currently has limited pharmacological options.
The REMS programme required for MYQORZO in obstructive HCM, which mandates regular echocardiographic monitoring given the heart failure risk, is expected to apply in the nHCM setting as well. Cardiologists and payers will scrutinise the LVEF and heart failure adverse event rates before committing to routine prescribing, making the safety granularity in these analyses commercially as well as clinically important. Cytokinetics also has two additional myosin-targeted compounds in development, omecamtiv mecarbil and ulacamten, signalling an ambition to build a franchise across the spectrum of cardiac muscle dysfunction.