ESC Congress Study Highlights Safety of Aficamten in Hypertrophic Cardiomyopathy

At the European Society of Cardiology (ESC) Congress 2024, the cardiology community received its deepest insights yet into the potential of aficamten in the management of hypertrophic cardiomyopathy ahead of the anticipated Q3 submission to the US Food and Drug Administration, including an integrated safety analysis leveraging data from the REDWOOD-HCM, SEQUOIA-HCM, and FOREST-HCM trials.^1,2

The study cohort included 170 patients with aficamten and 153 patients treated with placebo from the REDWOOD-HCM and SEQUIOA-HCM trials for the placebo-controlled pool. When including the FOREST-HCM cohort, investigators obtained data from 283 patients, including 100 who transitioned from placebo to aficamten.¹

Among the placebo-controlled pool, the mean cumulative follow-up was 70.8 patient-years on aficamten and 66.3 patient-years on placebo. The total cumulative exposure period to aficamten was 205.2 patient-years.¹

Upon analysis, treatment-emergent serious adverse events were identified among 10 (5.9%) aficamten patients and 14 (9.2%) placebo patients in the placebo-controlled pool. Among the cumulative exposure group, 24 (8.5%) aficamten patients experienced a treatment-emergent adverse event. During the blinded phase of the trials, adverse events reported by patients included dizziness (6.5% for aficamten vs 2% for placebo), syncope (1.8% for aficamten vs 2.6% for placebo), dyspnea (6.5% for aficamten vs 5.2% for placebo) and hypertension (6.5% for aficamten vs 2.6% for placebo).¹

Additionally, investigators noted site-read left ventricular ejection fraction (LVEF) dips to less than 50% resulting in down-titration occurred among 9 (5.3%) patients receiving aficamten (Exposure adjusted incidence rate [EAIR], 11.2 per 100 patient-years) and 1 (0.7%) placebo patient (EAIR, 1.3 per 100 person-years). A total of 11 (3.9%) aficamten patients in the cumulative pool experienced such an event (EAIR, 5.3 per 100 patient-years). Of note, none of the events where LVEF dipped to less than 50% events in aficamten patients were associated with heart failure symptoms.¹

During the maintenance phase of the cumulative exposure pool, a total of 1588 echocardiograms were performed. Of these, only 11 (0.7%) led to dose reduction due to LVEF less than 50%, with none resulting in discontinuation or treatment interruption. Furthermore, the cumulative pool contained 6 (2.1%) patients who terminated treatment early, but none were due to aficamten-related adverse events.¹

For more on this study, check out our interview with presenting investigator Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University.

Relevant disclosures for Masri include Cytokinetics, Bristol Myers Squibb, Eidos, Pfizer, Ionis, Lexicon, AstraZeneca, Tenaya, and others.

References:

1. A Masri, R Barriales-Villa, P Elliott, et al. Aficamten in patients with obstructive hypertrophic cardiomyopathy: an integrated safety analysis. Presented at: European Society of Cardiology Congress 2024. August 30 - September 2, 2024. London, UK.
2. Cytokinetics, Inc. Cytokinetics announces initiation of phase 1 study of Aficamten in healthy Japanese participants. Cytokinetics, Inc. June 17, 2024. Accessed September 3, 2024. https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-announces-initiation-phase-1-study-aficamten.