Cytokinetics aficamten data show structural heart benefits in HCM
Cytokinetics has presented additional data from two Phase 3 trials of aficamten (MYQORZO) at the European Society of Cardiology Congress in Munich, with analyses published simultaneously in Circulation and JACC: Heart Failure. The results extend the evidence base for the cardiac myosin inhibitor beyond its existing approved indication in obstructive hypertrophic cardiomyopathy (oHCM), pointing to clinically meaningful effects in the non-obstructive form of the disease for which no approved therapy currently exists.
The exploratory analysis from ACACIA-HCM examined echocardiographic endpoints in 517 patients with symptomatic non-obstructive HCM (nHCM) treated with aficamten or placebo over up to 72 weeks. At 36 weeks, aficamten significantly improved measures of diastolic function including peak E velocity (p=0.001) and septal e' velocity (p<0.001), suggesting enhanced myocardial relaxation and early diastolic filling. Left atrial volume index showed a statistically significant improvement at end of treatment (p=0.022), and left ventricular wall thickness decreased by 0.2 cm (p<0.001). The company says these structural findings support diastolic dysfunction as the probable mechanism underlying the functional and symptomatic benefits previously reported as the trial's co-primary endpoints.
Aficamten was associated with a modest reduction in left ventricular ejection fraction, though the company noted it remained within normal range throughout the extended treatment period.
Beating the standard of care in obstructive HCM
The post-hoc analysis from MAPLE-HCM, which enrolled 175 patients in a head-to-head comparison with the beta blocker metoprolol, examined whether prior treatment history influenced outcomes. Aficamten outperformed metoprolol on peak oxygen uptake regardless of whether patients had previously been taking a beta blocker. Among patients naive to beta blockers, aficamten produced a least-squares mean improvement in pVO2 of 3.1 mL/kg/min versus metoprolol (p<0.001); in those previously on a beta blocker, the advantage was 1.9 mL/kg/min (p<0.001), with no statistically significant interaction between the subgroups (p=0.133). Secondary endpoints including KCCQ Clinical Summary Score, NYHA functional class, LVOT gradient and NT-proBNP all favoured aficamten across both pre-trial treatment groups, and the safety profile was consistent with prior reports.
Stephen Heitner, Cytokinetics' chief medical officer, said the new findings "elaborate on the primary results from each trial and expand the body of evidence supporting the potential use of aficamten across the spectrum of HCM."
Regulatory path and competitive context
Cytokinetics plans to submit a Supplemental New Drug Application for aficamten in nHCM in the fourth quarter of 2026, building directly on the ACACIA-HCM programme. Approval in this indication would represent a meaningful commercial expansion: roughly half of the estimated one-in-350 people living with HCM worldwide have the non-obstructive subtype, a population currently managed off-label with symptom-directed therapies such as beta blockers and calcium channel blockers.
The HCM space has become significantly more competitive since mavacamten (Bristol Myers Squibb's Camzyos) received FDA approval in 2022. Cytokinetics is differentiating aficamten on a cleaner pharmacokinetic profile and the breadth of its clinical programme, which now spans oHCM, nHCM, a paediatric cohort in CEDAR-HCM, and an open-label extension study in FOREST-HCM. The MAPLE-HCM head-to-head data against metoprolol are particularly useful commercially, as most patients with oHCM are managed on beta blockers before specialist referral; demonstrating consistent superiority irrespective of prior treatment history removes a potential prescriber objection.
Both the nHCM sNDA filing timeline and the competitive landscape around myosin inhibitors will be closely watched heading into late 2026.