New 96-week data from the FOREST-HCM trial is shedding further light on the potential of aficamten among patients with
Presented at the
“These long-term data from FOREST-HCM demonstrate that, for 2 years, aficamten was well tolerated in these nHCM patients, with most achieving the highest available dose and demonstrating sustained improvements in heart failure symptoms and marked improvements in cardiac biomarkers,” wrote investigators. “Although this is an open-label trial, the magnitude of benefit observed on NYHA class and KCCQ-CSS likely exceeds that observed in placebo groups previously.”
Aficamten, alongside fellow cardiac myosin inhibitor mavacamten (Camzyos), has been touted by many as a game-changing innovation with potential to revolutionize management of hypertrophic cardiomyopathies. At the time of presentation at HFSA 2025, Cytokinetics is awaiting a decision from the US Food and Drug Administration regarding its New Drug Application for aficamten, which has been assigned a PDUFA date of December 26, 2025.
Although mavacamten boasts an approval for oHCM, the field has turned to aficamten as their next great hope for nHCM as Bristol Myers Squibb announced the phase 3 ODYSSEY-HCM trial in nHCM had missed its primary endpoint. The phase 3 trial for aficamten in nHCM, named ACACIA-HCM, is expected to read out in the first half of 2026.
Data from 34 patients in FOREST-HCM were presented at HFSA 2025. These patients received aficamten beginning at 5 mg daily with titration in 5-mg increments (up to 20 mg) based on serial left ventricular ejection fraction (LVEF) assessment. By week 6, 82.4% of participants were on 15 mg or 20 mg, with dose stability maintained throughout the 96-week study period.
Symptom and Functional Class Improvement
- Mean Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (KCCQ-CSS) improved by 11.2 (SD, 14.3) points from baseline (P < 0.0001).
- 64.7% of patients achieved ≥5-point improvement, considered clinically meaningful.
- New York Heart Association functional class improved by at least 1 class in 79.4% of patients, and 74.1% of those improved became asymptomatic by week 96.
- The proportion of patients with NYHA class III symptoms decreased from 41.2% at baseline to 11.8% at 96 weeks, highlighting sustained functional gains.
When examining changes in biomarker and cardiac function, investigators noted NT-proBNP levels showed a consistent, statistically significant decrease from baseline at each visit (P <.0001), reflecting reduced wall stress, and high-sensitivity cardiac troponin I levels decreased significantly, suggesting reduced myocardial injury. Additionally, investigators pointed out LVEF decreased modestly from hyperdynamic baseline values into the normal range by week 12, remaining stable through week 96.
Safety data from the trial indicated no patients permanently discontinued aficamten. However, investigators noted 4 patients experienced LVEF less than 50%, all at the highest doses (15–20 mg), which were reversible with down-titration or temporary interruption. Of these 4, 2 had been previously reported and the 2 new cases occurred during the ensuing 60 weeks, with both being asymptomatic. Investigators also noted all 4 demonstrated reversibility after downtitration or short-duration interruption.
“Taken together, this 96-week overview of aficamten treatment for patients with symptomatic nHCM in FOREST-HCM provides support for the ongoing, pivotal randomized controlled trial ACACIA-HCM,” wrote investigators.
References:
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Masri A. Safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy: a 96-week analysis from FOREST-HCM. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.
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Bristol Myers Squibb. Bristol Myers Squibb Provides Update on Phase 3 ODYSSEY-HCM Trial. Bms.com. Published April 15, 2025. Accessed September 28, 2025.
https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-ODYSSEY-HCM-Trial/default.aspx