Open-Label Study Finds Aficamten Could Help Most oHCM Patients Avoid Surgery

New data from the FOREST-HCM trial suggests use of aficamten could help patients with obstructive hypertrophic cardiomyopathy (oHCM) avoid needing to undergoing septal reduction therapy (SRT).

Presented at American Heart Association (AHA) Annual Scientific Sessions 2024, data from a subgroup analysis of the trial suggested 97% of SRT-eligible patients included in the trial were no longer eligible after 24 weeks of treatment with aficamten.

“This is an open level study, so you can't always take everything from it and say, ‘I have the highest level of evidence [and] that this is being achieved’. However, what I would argue is day in, day out, in the clinic, this is what we use to treat patients,” explained Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, in an interview with HCPLive. “We use their symptoms, their LVOT gradient, how they feel, my impression or the physician's impression of what's going on, and we recommend to them surgery or no surgery.”

An ongoing trial, FOREST-HCM is an open-label extension study of patients from the phase 2 REDWOOD-HCM or SEQUOIA-HCM trials. In the AHA 2024 analysis, investigators presented data on the effects among a subgroup of patients considered eligible for SRT from the study. Among the 180 patients with oHCM with at least 24 weeks of follow-up, 31.6% (n=57) were considered eligible for SRT at baseline.

Upon analysis, investigators found just 3.5% (n=2) of this subgroup remained eligible for SRT after 24 weeks of treatment. Investigators highlighted 35.1% (n=20) had a left ventricular outflow obstruction (LVOT) gradient of 50 mmHg or greater but were NYHA Class I/II and 3.5% (n=2) had NYHA III/IV but LVOT gradient less than 50 mmHg.

Further analysis suggested 92.9% (n=52) of SRT-eligible patients, as well as 67.8% of the remaining cohort, improved at least 1 NYHA class during by week 24. Additionally, investigators called attention to results indicated greater improvements were observed among SRT-eligible patients relative to those in remaining cohort (21.7 [SD, 19.3] vs 13.5 [SD, 13.9]; P = .003).

For more on this study and how it informs clinicians on the effects of aficamten among patients with oHCM, check out our interview with Masri from the floor at AHA 2024.

Relevant disclosures for Masri include Cytokinetics, Bristol Myers Squibb, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, BioMarin, and AstraZeneca.

References:

Masri A. Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.