Additional 48-week data From FOREST-HCM, the open label extension clinical study of aficamten, presented at The American College of Cardiology 73rd Annual Scientific Session.- Cytokinetics Inc.,

Cytokinetics, Incorporated announced additional 48-week data from FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) , the open label extension clinical study of aficamten in patients with hypertrophic cardiomyopathy (HCM), at the 73rd Annual American College of Cardiology (ACC) Scientific Session taking place from April 6, 2024 –April 8, 2024 in Atlanta, GA.

FOREST-HCM enrolled 213 patients with obstructive HCM from May 28, 2021 through October 31, 2023. Previously presented data from 17 patients who had been enrolled through 48 weeks in FOREST-HCM showed that prolonged treatment with aficamten was associated with significant and sustained reductions in left ventricle outflow tract gradient (LVOT-G), and improvements in symptoms and cardiac biomarkers. The updated data set presented at ACC in Atlanta focuses on 46 patients from FOREST-HCM that had completed 48 weeks of follow-up at the time of the current interim analysis.

At Week 48, 75% of these patients were receiving the 15 mg or 20 mg dose of aficamten. Treatment with aficamten for 48 weeks resulted in substantial and sustained reductions in average resting LVOT-G (mean change from baseline (SD) = -39.6 mmHg (34), p<0.0001) and valsalva lvot-g (mean change from baseline (sd)="-53.2" mmhg (38.6), p><0.0001). statistically significant improvements in new york heart association (nyha) functional class from baseline were observed, with 82.2% of patients improving by greater than 1 nyha class with no instances of worsening nyha class. additionally, there were significant improvements in nt-probnp, a biomarker of cardiac wall stress, with an average decrease of 63% from baseline to week 48 (p><0.001).>

Treatment with aficamten also resulted in statistically significant improvements in measures of cardiac structure and function including decreases in maximum wall thickness (mean change from baseline (SE) = -0.12 cm (0.02), p<0.0001), left atrial volume index (mean changes from baseline (se)="-3.5" ml m2 (0.98), p="0.0008)" and lateral e e’ (mean change from baseline (se)="-2.2" (0.92), p="0.02)." while 19 of these 46 patients in forest-hcm met guideline eligibility criteria for septal reduction therapy (srt) at baseline, only one patient remained eligible for srt after six months of treatment with aficamten, representing a 94% reduction in srt-eligibility.>

In FOREST-HCM, aficamten appears to be well-tolerated, with no treatment-related serious adverse events (SAEs). There was a modest reduction in left ventricular ejection fraction (LVEF) from baseline to Week 48 (mean change from baseline (SD) = -5.1 mg (5.9), p<0.0001). as has been previously reported, three patients underwent dose down-titration due to lvef><50%. two patients were asymptomatic, and one dose down-titration occurred due to recurrent alcohol-induced atrial fibrillation.>

“These data from FOREST-HCM continue to reinforce the efficacy and safety of longer-term treatment with aficamten for patients with obstructive HCM, demonstrating significant improvements in patient symptom burden and cardiac function while also improving the overall architecture of the heart,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “In light of the positive results from SEQUOIA-HCM, the pivotal Phase III clinical trial of aficamten, we are pleased to see this additional clinical evidence that reinforces our intended next-in-class profile and that may enable aficamten to become the cardiac myosin inhibitor of choice among physicians and patients with HCM.”