Promising Findings from Aficamten's FOREST-HCM Study Revealed in 48-Week Additional Data

Aficamten, a selective small molecule cardiac myosin inhibitor, has shown significant potential in the treatment of hypertrophic cardiomyopathy (HCM). Recently, Cytokinetics, in collaboration with J-Star Pharmaceuticals, presented additional 48-week data from the FOREST-HCM study at the 73rd Scientific Session of the American College of Cardiology (ACC). The study aims to evaluate the long-term efficacy and safety of aficamten in patients with obstructive HCM. The newly unveiled data showcase promising outcomes in clinical endpoints, NYHA classification, cardiac biomarkers, and cardiac structure and function.

Key Findings:

The FOREST-HCM study enrolled 213 patients with obstructive HCM from May 28, 2021, to October 31, 2023. Previously released data from 17 patients who completed 48 weeks of aficamten treatment demonstrated a sustained reduction in left ventricular outflow tract gradient (LVOT-G), improvement in symptoms, and cardiac biomarkers. The latest dataset presented at the ACC meeting included 46 patients who completed 48 weeks of follow-up. Notably, 75% of patients received either a 15 mg or 20 mg dose of aficamten.

After 48 weeks of treatment with aficamten, there was a significant and sustained decrease in both resting LVOT-G (mean change [SD] = -39.6 mmHg [34], p<0.0001) and Valsalva LVOT-G (mean change [SD] = -53.2 mmHg [38.6], p<0.0001) compared to baseline. Improvement in New York Heart Association (NYHA) functional classification was statistically significant, with 82.2% of patients experiencing an increase of ≥1 NYHA class, and no cases of NYHA deterioration were reported. Additionally, the cardiac biomarker NT-proBNP exhibited a significant improvement, with an average reduction of 63% from baseline to week 48 (p<0.001).

Aficamten treatment also resulted in significant improvements in cardiac structure and function parameters. These included a reduction in maximum wall thickness (mean change [SE] = -0.12 cm [0.02], p<0.0001), decreased left atrial volume index (mean change [SE] = -3.5 mL/m2 [0.98], p=0.0008), and lowered lateral wall E/e' (mean change [SE] = -2.2 [0.92], p=0.02). In the subset of 46 patients from the FOREST-HCM study, 19 patients initially qualified for septal reduction therapy (SRT) at baseline. However, after 6 months of aficamten treatment, only one patient remained eligible for SRT, indicating a 94% reduction in patients meeting SRT criteria.

Safety and Tolerability:

The tolerability of aficamten in the FOREST-HCM study was favorable, with no treatment-related serious adverse events (SAEs) reported. A slight decrease in left ventricular ejection fraction (LVEF) was observed from baseline to week 48 (mean change [SD] = -5.1 mg [5.9], p<0.0001), and three patients required dose adjustments due to LVEF < 50%. Two patients remained asymptomatic, while one patient experienced recurrent alcohol-induced atrial fibrillation, leading to a reduction in dosage.

Aficamten's 48-week additional data from the FOREST-HCM study provide encouraging evidence of its potential as a treatment option for patients with HCM. The study demonstrated significant and sustained improvements in clinical endpoints, NYHA classification, cardiac biomarkers, and cardiac structure and function. These findings support the ongoing development of aficamten as a novel cardiac myosin inhibitor, offering hope for enhancing exercise capacity, alleviating disease symptoms, and exerting long-term effects on cardiac health in HCM patients.