Cytokinetics demonstrates first efficacy of treatment for rare cardiomyopathy

Cytokinetics’ cardiac myosin inhibitor Myqorzo (active ingredient aficamten) has demonstrated significant treatment efficacy for the first time in patients with nonobstructive hypertrophic cardiomyopathy (nHCM).

According to Fierce Pharma, a U.S. pharmaceutical industry publication, on the 28th local time, Cytokinetics will present detailed data from the phase 3 ACACIA trial at the European Society of Cardiology (ESC) annual congress, which will be held in Munich, Germany, this weekend.

nHCM is a rare disease in which the heart’s pumping muscle becomes thick and stiff, preventing it from filling properly with blood. Until now, standard treatment has been based only on estimates drawn from results of other large-scale cardiac trials.

According to the clinical results, the Myqorzo group’s score on the KCCQ-CSS, a questionnaire assessing symptoms of heart disease, improved by 3 points more than the placebo group at week 36. Patients who continued treatment through week 72 showed a 7-point difference.

Peak oxygen consumption (pVO2), which reflects maximum exercise capacity, also improved by 0.67ml/kg/min versus placebo at week 36. Because the company considers an increase of just 0.35 in studies of obstructive hypertrophic cardiomyopathy (oHCM) sufficient to begin producing functional improvement, the current result is approximately twice that benchmark.

Steven Heitner, chief medical officer (CMO) of Cytokinetics, told Fierce Pharma, “Patients reported feeling better and were objectively able to exercise more than those receiving placebo.”

When treatment was stopped for 4 weeks after the end of week 72, KCCQ-CSS scores in the Myqorzo group rapidly fell to the level of the placebo group. Heitner, the CMO, described this as a “reverse proof” of the drug’s effect.

Significant improvements were also observed in secondary endpoints, including New York Heart Association (NYHA) functional class and NT-proBNP, a marker of cardiac stress.

This success contrasts with Bristol Myers Squibb’s (BMS) Camzyos, which fell short of expectations in a similar nHCM trial last year. Camzyos was first launched in 2022 for the oHCM indication, while Myqorzo was approved for the same indication in 2025.

If the nHCM indication is added, the patient population eligible for Myqorzo prescriptions could nearly double. Heitner, the CMO, said that the prevalence of nHCM has been reported at between 1 in 200 and 1 in 500 people.

In terms of safety, Myqorzo was generally well tolerated. However, the rate of early treatment discontinuation due to adverse events was higher in the Myqorzo group, at 7%, than in the placebo group, at 1.9%.

Myqorzo has carried a boxed warning about the risk of heart failure since its approval in 2025, and the company is operating the risk evaluation and mitigation strategy (REMS) required by the U.S. Food and Drug Administration (FDA).

In the trial, only 2 patients (0.8%) in the Myqorzo group progressed to heart failure related to the drug’s relaxation effect. Twenty-seven participants (10.5%) had a left ventricular ejection fraction (LVEF) below the threshold of 50%, and 21 of them continued in the trial after dose adjustment.

However, 10 additional cases of heart failure unrelated to LVEF reduction occurred in the Myqorzo group, compared with 3 in the placebo group, showing an imbalance. All heart failure cases occurred early in the trial during the dose-titration phase.

Heitner, the CMO, attributed this to initial prescribing decisions made by an artificial intelligence (AI) algorithm that adjusted doses based solely on ejection fraction. In an extension study in which physicians made the prescribing decisions, heart failure unrelated to ejection fraction decreased to 2 cases among 390 patients.

Based on the ACACIA data, Cytokinetics plans to apply to the FDA for approval of the additional nHCM indication by the end of the fourth quarter. Myqorzo is currently marketed in the United States and China as a treatment for oHCM, and it has also been approved in the United Kingdom and European Union (EU), with a sequential launch beginning in Germany last June.