Sara Saberi, MD: FOREST-HCM Data Demonstrates Long-Term Effects of Aficamten

Data from a 46-person cohort with 1 year of follow-up from the FOREST-HCM trial provides clinicians with further insight into the long-term effects of aficamten in patients with hypertrophic cardiomyopathy.

Presented at the American College of Cardiology 2024 (ACC.24) Annual Scientific Sessions, the latest data from the FOREST-HCM study details significant and sustained reductions in left ventricle outflow tract gradient (LVOT-G), and improvements in symptoms and cardiac biomarkers with use of aficamten, a cardiac myosin inhibitor from Cytokinetics.¹

“What we are seeing is actually a rapid, pretty robust and sustained reduction in outflow obstruction with maintenance of LV systolic function over that time period, along with significant improvements in how patients report to us that they feel in terms of assessments by KCCQ,” said lead investigator Sara Saberi, MD, associate professor of Internal Medicine at University of Michigan Health Frankel Cardiovascular Center, in an interview with HCPLive.

An ongoing trial, FOREST-HCM is an open-label extension study of patients from the REDWOOD-HCM or SEQUOIA-HCM trials. As of April 05, 2024, the trial includes more than 200 participants, with 46 patients having achieved at least 48 weeks of follow-up at the time of the interim analysis presented at ACC.24.^2,3

Follow-up data from this cohort suggested use of aficamten was associated with significant and sustained reductions in average resting LVOT-G (mean change from baseline, -39.6 mmHg [Standard deviation, 34]; P <.0001) and Valsalva LVOT-G (mean change from baseline, -53.2 mmHg [SD, 38.6]; P <.0001). Further analysis indicated use was associated with statistically significant improvements in New York Heart Association (NYHA) Functional Class from baseline, with 82.2% of patients improving by 1 or more NYHA class with no instances of worsening NYHA class observed among this cohort. 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 <.001).¹

Investigators highlighted 19 of the 46 patients included in this analysis were considered eligible for septal reduction therapy at baseline, but only 1 patient remained eligible after 6 months. Additionally, no treatment-related serious adverse events were reported in the trial, with a modest reduction in left ventricular ejection fraction from baseline to Week 48 (mean change from baseline, -5.1 mg [SD, 5.9]; P <.0001).¹

For more insight into the findings and what they mean for clinicians as they await further data from the aficamten program, check out our interview with Saberi from the conference floor at ACC.24.

Relevant disclosures for Saberi include Cytokinetics and Bristol-Myers Squibb Company.

References:

1. Saberi S, Abraham TP, Choudhury L, et al, Hutchinson HG, Wolski K et al. EFFICACY AND SAFETY OF AFICAMTEN IN THE FIRST COHORT OF PATIENTS WITH SYMPTOMATIC OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY COMPLETING 1-YEAR FOLLOW-UP: FINDINGS FROM THE FOREST-HCM STUDY. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
2. Cytokinetics, Inc. Cytokinetics presents additional 48-week data from Forest-HCM, the Open Label Extension Clinical Study of AFICAMTEN, at the American College of Cardiology 73rd annual scientific session. Cytokinetics, Inc. April 5, 2024. Accessed April 11, 2024. https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-presents-additional-48-week-data-forest-hcm-open.
3. Hypertrophic cardiomyopathy clinical trials: Aficamten. Cytokinetics. April 10, 2024. Accessed April 11, 2024. https://cytokinetics.com/medicines-research/hypertrophic-cardiomyopathy-clinical-trials/.