Cytokinetics aficamten clears both endpoints in 517-patient heart trial

Cytokinetics' aficamten improved symptoms and exercise capacity in a 517-patient Phase 3 trial of non-obstructive hypertrophic cardiomyopathy, a genetic heart condition with no approved treatments, clearing the path for a fourth-quarter US filing.

"ACACIA-HCM is the first-ever positive clinical trial in non-obstructive HCM," Stephen Heitner, chief medical officer at Cytokinetics, said.

The drug met both dual primary endpoints at 36 weeks. Kansas City Cardiomyopathy Questionnaire scores rose 11.4 points versus 8.4 for placebo (p=0.021), while peak oxygen consumption climbed 0.64 ml/kg/min against a 0.03 decline (p=0.003). Results held across all prespecified subgroups, including patients with atrial fibrillation and those on background beta-blockers.

If approved, aficamten would be the first therapy for nHCM, which accounts for roughly half of the estimated 1-in-350 people worldwide with hypertrophic cardiomyopathy. Cytokinetics plans to submit a supplemental new drug application to the FDA in the fourth quarter.

First mover in a market with no standard of care

The results, presented Friday at the European Society of Cardiology Congress in Munich and published in the New England Journal of Medicine, position Cytokinetics to challenge Bristol Myers Squibb's Camzyos (mavacamten), the only other cardiac myosin inhibitor on the market, which is cleared solely for the obstructive form of the disease. Aficamten works by reducing cardiac contractility through myosin inhibition, easing the stiff, thickened heart muscle that defines HCM.

Secondary endpoints also favored aficamten. More patients improved at least one New York Heart Association functional class (41.9 percent versus 27.8 percent, p<0.001), and the drug cut NT-proBNP, a biomarker of cardiac wall stress, by 57 percent relative to placebo. A global efficacy analysis published in Circulation found 53 percent of aficamten patients showed clinical response in three or more of five disease domains, versus 13 percent on placebo.

Safety profile and the road to approval

The drug was generally well tolerated, though left ventricular ejection fraction fell below 50 percent in 27 aficamten patients (10.5 percent) versus two on placebo (0.8 percent). Serious adverse events occurred in 20.2 percent of treated patients versus 14.7 percent on placebo, with heart failure events concentrated during the first 12 weeks of dose titration and generally responsive to diuretics.

Cytokinetics, which took 27 years to win its first regulatory approval, already sells MYQORZO for obstructive HCM in the US, China, the European Union and the UK. The company is also studying aficamten in children with obstructive HCM and in FOREST-HCM, an open-label extension, while advancing omecamtiv mecarbil and ulacamten in earlier-stage heart failure programs.

Shares rose 1.3 percent in premarket trading Friday. The nHCM expansion could roughly double the drug's addressable patient pool, though some analysts have called the symptom benefit modest. Cytokinetics did not disclose a cash runway figure in the release.

This article is for informational purposes only and does not constitute investment advice.