Cytokinetics drug aficamten met the main goal of a pivotal test in obstructive hypertrophic cardiomyopathy. If approved, the daily pill would compete against a Bristol Myers Squibb drug projected to become a blockbuster seller.

By FRANK VINLUAN
An experimental Cytokinetics drug has Phase 3 data showing it improved the ability of the heart to work during exercise. In addition to meeting this main goal of its pivotal test in a rare cardiovascular disease, the results look competitive with a Bristol Myers Squibb product already on the market.

The Cytokinetics drug, aficamten, is a potential treatment for obstructive hypertrophic cardiomyopathy (oHCM), a condition that leads to thickening of heart muscle that makes it harder for the organ to pump blood. Patients experience fatigue and shortness of breath. The condition can progress to heart failure.

Cytokinetics reported preliminary Phase 3 results on Wednesday showing that after 24 weeks, treatment with its once-daily pill led to a 1.74 point increase in peak oxygen uptake during exercise compared to a placebo. The study had a targeted enrollment of 270 patients. South San Francisco-based Cytokinetics said the treatment effect was consistent across patient subgroups, including those receiving or not receiving beta blockers, a type of blood pressure drug also used to manage oHCM.

Secondary goals included assessments of cardiomyopathy and heart function at weeks 12 and 24. Cytokinetics reported statistically significant and clinically meaningful improvement on these measures, but did not disclose specific figures.

In oHCM, genetic mutations affect myosin, a heart muscle protein. Mutated myosin lead to excessive contractions that thicken the heart muscle. Aficamten is a small molecule designed to bind to myosin, stabilizing the protein in a state in which it is unable to turn chemical energy into movement that becomes heart muscle contractions.

BMS drug Camzyos works similarly to aficamten. The pharmaceutical giant added its oHCM molecule to its pipeline via a $13.1 billion acquisition and the drug is projected to become a blockbuster seller. In the nine months ended Sept. 30, BMS reported the product accounted for $143 million in revenue compared to $8 million in the same period in 2022, the year of the medication’s FDA approval.

One problem for Camzyos is it can also reduce the volume of blood the heart’s left ventricle pumps with each contraction, potentially leading to heart failure. The drug’s label flags this left ventricular ejection fraction (LVEF) risk, which must be managed by a Risk Evaluation and Mitigation Strategy (REMS), a program that imposes strict oversight and monitoring of the use of a drug.

Cytokinetics said aficamten was well tolerated with an adverse event profile comparable to placebo. The company reported that five patients (3.5%) in the treatment group developed low LVEF compared to one (0.7%) in the placebo group. But there were no reports of worsening heart failure or treatment interruptions. Cross-trial comparisons can be misleading, but Camzyos’s Phase 3 test posted results showing seven patients in the treatment group and two in the placebo arm experienced reductions in LVEF.

“A therapy like aficamten that improves exercise capacity in a clinically meaningful manner, absent low LVEF events that interrupt treatment, should be a welcome addition for HCM patients as well as the clinicians who treat them,” Martin Maron, director of the Hypertrophic Cardiomyopathy Center, Lahey Hospital and Medical Center in Burlington, Massachusetts, and national director of aficamten’s Phase 3 test, said in a prepared statement.

In a research note sent to investors Wednesday, Leerink Partners analyst Roanna Ruiz wrote that aficamten’s consistent treatment effect across patient subgroups could support broader use of the drug in oHCM. She added that the safety profile could support a less restrictive REMS program compared to Camzyos. The drug’s competitive potential has reportedly attracted takeover interest from at least two big pharma companies.

Cytokinetics said full results from aficamten’s Phase 3 study will be presented at an upcoming medical conference.

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