A new HFpEF treatment might be on the horizon, after results from the EMBARK-HFpEF trial showed that BMS’ hypertrophic cardiomyopathy treatment, mavacamten (Camzyos), safely improved key HFpEF symptoms and biomarkers.
- Mavacamten is the only cardiac myosin inhibitor with FDA approval to treat obstructive HCM, and works by reducing heart muscle contraction and improving blood flow.
- That action could also help treat HFpEF, a disease with limited treatment options.
To test mavacamten’s HFpEF potential, the open-label Phase 2a EMBARK-HFpEF trial treated 30 HFpEF patients with mavacamten (avg age 76, NYHA Class II & III, LVEF ≥60%), finding notable 26-week improvements to…
- NTproBNP: −26%
- hsTnT: −13%
- hsTnI: −20%
- NYHA class: 41.7% of measured patients
These improvements regressed to baseline over the study’s eight-week washout period, indicating a true treatment effect.
Although there were no unexpected safety events, the trial did reveal LVEF concerns that are typical with cardiac myosin inhibitors. The patients had a 3.2 percentage point average LVEF reduction, and three of the patients had to interrupt mavacamten due to LVEF declines.
The authors were encouraged by the EMBARK-HFpEF trial, which might be small and open-label, but appears to show that cardiac myosin inhibitors have a positive effect on HFpEF patients, particularly those with LVEF at the high-end of normal.
- Mavacamtem’s apparent effectiveness among patients with LVEF over 60% might be notable, given that these patients are believed to see less benefits from the major neurohormonal HFpEF therapies.
The trial also adds anticipation for BMS’ slightly larger AURORA-HFpEF Phase 2a double-blinded RCT, which will further evaluate the safety, tolerability, and exposure-response of a next-generation cardiac myosin inhibitor, MYK-224, in patients with symptomatic HFpEF.
The Takeaway
Mavacamten still has a lot to prove, but these initial results show that it does address key HFpEF biomarkers and symptoms, with a similar safety profile as its widely accepted use among HCM patients.
