CYTK Myqorzo: First-Ever Phase 3 Win in Non-Obstructive HCM

Cytokinetics presented full Phase 3 data for Myqorzo (aficamten) in non-obstructive hypertrophic cardiomyopathy at the ESC Congress, and the headline holds: it is the first positive Phase 3 result ever recorded in nHCM. The topline from May 5 already confirmed the drug met both co-primary endpoints; the ESC presentation added the specific numbers, published simultaneously in the New England Journal of Medicine. The stock closed at $77.90.

Aficamten is a cardiac myosin inhibitor, a drug that damps the overactive heart-muscle contraction that drives hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is the most common inherited heart condition, affecting an estimated 400,000 to 800,000 people in the US, and roughly one-third have the non-obstructive form where blood flow is not blocked but the muscle is still thickened and stiff.

In ACACIA-HCM, a trial of 516 patients, aficamten improved peak oxygen consumption by 2.2 mL/kg/min versus placebo while lifting the Kansas City Cardiomyopathy Questionnaire score by 8.3 points (p<0.001). NT-proBNP, a biomarker of heart strain, fell 59.2%. The pVO2 benefit was nearly identical in men and women, with women making up 42% of the trial, addressing a known gap in HCM research. More than four in ten aficamten patients improved at least one NYHA functional class versus 27.8% on placebo, and left-atrial mechanics improved, a signal of the diastolic relief these patients need.

The victory is notable because the class leader already failed here. Bristol Myers Squibb’s mavacamten (Camzyos) missed its nHCM trial, ODYSSEY-HCM, leaving aficamten alone in a population with no approved drug. In nHCM, symptom burden stems from diastolic dysfunction rather than outflow-tract obstruction, which is why the mechanism translated unevenly across the class.

The safety caveat is the same one that boxed the class. Left ventricular ejection fraction fell below 50% in 10.5% of aficamten-treated patients versus 0.8% on placebo, consistent with the boxed warning on Myqorzo’s obstructive-HCM label. Most of those patients stayed on the drug at the same or a lower dose.

Cytokinetics plans to file a supplemental NDA for nHCM in Q4 2026. That filing is separate from the already-accepted MAPLE-HCM sNDA for obstructive HCM, which carries a PDUFA date of November 14, 2026. If the nHCM filing lands on schedule, aficamten could become the first drug cleared to treat both forms of HCM, a franchise expansion that would widen Myqorzo’s addressable market well beyond its current obstructive-only label. The near-term test is whether the FDA accepts the nHCM filing without asking for more data, given the ejection-fraction signal. The cardiometabolic catalysts worth tracking this year.

Source: Cytokinetics press release