Cytokinetics spent Labor Day weekend in Spain, sharing a big phase 3 win for its lead cardio candidate at the European Society of Cardiology Congress in Madrid.
A daily pill of small molecule aficamten improved oxygen capacity by 1.1 milliliters per kilogram per minute in patients with genetic heart enlargement, easily besting the 1.2-point loss in patients given a standard-of-care beta blocker, the biotech announced in an Aug. 30 release.
The results were published in The New England Journal of Medicine on the same day.
The phase 3 Maple-HCM trial enrolled 175 patients with obstructive hypertrophic cardiomyopathy (oHCM), a condition in which the heart wall thickens and blocks blood flow. The study compared aficamten, a cardiac myosin inhibitor, with the beta blocker metoprolol.
The trial was designed to enroll patients with less severe HCM than aficamten’s registrational phase 3 trial Sequoia-HCM, Cytokinetics said in the release.
“These results demonstrate that aficamten meaningfully improves exercise capacity in patients with obstructive HCM while treatment with metoprolol resulted in a meaningful reduction in exercise capacity,” Fady Malik, M.D., Ph.D., Cytokinetics’ executive vice president of research and development, said in the release. “Importantly, these effects were achieved in a broader patient population with oHCM than previously studied in SEQUOIA-HCM.”
The data sent Cytokinetics stock soaring, from $36.33 per share Aug. 29 to as high as $49.54 at 12:30 p.m. ET Sept. 2.
“Afi essentially performed as expected, but the relative underperformance of beta blockers—the de facto standard-of-care for almost 60 years—is eye opening,” analysts from Evercore ISI wrote in a Sept. 2 note. “This should trigger updates to treatment guidelines in both the U.S. and EU by around 2027.”
Clinical relevance for change in oxygen uptake is seen as 1 mL/kg/min, analysts from Mizuho wrote in a Sept. 1 note, meaning that aficamten “hit on absolute change” as well as beating metoprolol.
Another phase 3 trial, Acacia-HCM, is testing aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) and is set to conclude in June 2026. In nHCM, heart muscle is thickened, but not enough to block blood flow. At the same Madrid conference, Bristol Myers Squibb shared detailed data from the its own failed phase 3 trial in nHCM, which revealed the Big Pharma was closer to a win than previously thought.
The detailed data for BMS’ heart drug Camzyos (mavacamten), a myosin inhibitor already approved for oHCM, “suggests afi has a legit chance with its phase 3 ACACIA trial,” the Evercore analysts wrote. “If ACACIA were to hit, it would expand aficamten’s opportunity to a currently uncontested 30,000-40,000 symptomatic nHCM patients.”
The analysts from Mizuho agree on aficamten’s potential. “Afi may simply end up being a more simplified solution for both oHCM and nHCM, given efficacy/safety data-to-date,” the Mizuho analysts wrote, adding it'd be a "major win" for Cytokinetics if that were to happen.
The FDA is set to decide whether to approve aficamten for oHCM by Dec. 26. The PDUFA date was pushed back from Sept. 26 after the regulator unexpectedly asked for a Risk Evaluation and Mitigation Strategy plan from the biotech.