Cytokinetics, a San Francisco biotech company, is hoping that its experimental HCM drug, aficamten, will soon be a competitor to Bristol Myers Squibb’s first-in-class myosin inhibitor Camzyos (mavacamten). Aficamten is an oral cardiac myosin inhibitor which, like Camzyos, treats HCM by reducing the the excessive number of interactions between cardiac myosin proteins.

An earlier Phase 2 study called Redwood-HCM established the safety of the drug.  The positive results of Redwood-HCM led to the Phase 3 study entitled Sequoia – HCM.

Topline results of Sequoia-HCM were presented in late December of 2023, while primary results and data from the study were presented on May 13 at tthe European Society of Cardiology Heart Congress meeting held in Lisbon, Portugal.  The complete paper was published in the New England Journal of Medicine on May 13, 2024.

The Study:  The study enrolled 282 patients with obstructive HCM.  Half were assigned to the drug while half took a placebo drug instead.  The total period of observation for the study was 28 weeks.  Patients enrolled in the study took aficamten for 24 weeks, followed by a 4 week period for washout of the drug.  Patients in both groups were allowed to stay on background therapies including beta blockers, calcium channel blockers, and disopyramide.

Primary Endpoint:   The primary endpoint of the study, as well as all 10 secondary endpoints, were met with statistically meaningful results.  The primary endpoint showed an improvement to exercise capacity, quantified by an increase in peak oxygen uptake (pVO₂) as measured by cardiopulmonary exercise testing (CPET) on a treadmill or bike by 1.8 ml/kg/min over a period of 24 weeks.

The study results also met multiple secondary endpoints including:

Subjective Improvement in Symptoms:  Patients scores showed a 7 point increase on the Kansas City Cardiomyopathy Questionnaire.  This is a questionnaire that has been validated for measuring heart failure symptoms over time by asking individuals repeated questions about how they are feeling.

Improvement in functional capacity:  34% of patients experiencing ≥1 class improvement as measured by New York Heart Association (NYHA) class (which is determined by the medical team after observation and questioning).

Septal Reduction Therapy Eligibility:  Almost all of the patients who qualified for septal reduction therapy at the start of the study no longer qualified for invasive septal reduction therapies at the end (i.e. septal myectomy and septal alcohol ablation).

Safety:  Aficamten was found to be safe and well tolerated.  There was no need to interrupt treatment for heart failure when a patient’s ejection fraction fell below 50%.  If a patient’s ejection fraction (EF) did fall below 50%, the EF recovered either spontaneously or when the aficamten dosage was decreased.

No differences in response were seen in responders based on age, sex or usage of background drug therapies.

When will Aficamten be available to patients? 

Cytokinetics expects to file for regulatory approval in both the U.S. and Europe by the end of the 2024.  They hope that they will be able to bring the drug to market by the end of 2025, depending on the timing and results of the regulatory process.  The prescribing information and any restrictions surrounding use (i.e. the necessity and frequency of repeat echocardiograms and REMS program, both which are mandated for Camzyos) will also be determined by regulators.

For more about aficamten see these past blogs on HCMBeat:

Is Aficamten the Blockbuster Drug Cytokinetics is Hoping For?

Cytokinetics Teases Upcoming Phase 3 Aficamten Trial in nHCM

Promising Data about Aficamten Presented at Meetings

Aficamten Updates from Cytokinetics

More on Aficamten & Mavacamten from ACC 2022

Aficamten Gets “Breakthrough Drug” Status from FDA

Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron