Positive topline results were announced from a phase 3 study evaluating mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) who are eligible for septal reduction therapy (SRT).
Mavacamten is an oral, selective allosteric inhibitor of cardiac myosin. It reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.
The randomized, double-blind, placebo-controlled, multicenter VALOR-HCM trial (ClinicalTrials.gov Identifier: NCT04349072) is evaluating the effects of mavacamten in over 100 patients with symptomatic obstructive HCM (NYHA class III-IV) who met the guideline criteria for SRT and had been referred for an invasive procedure.
The trial includes 3 treatment periods over 128 weeks: a 16-week placebo-controlled period where patients are randomly assigned 1:1 to receive mavacamten or placebo; a 16-week active treatment period where all patients will receive mavacamten, and a 96-week long-term extension period where patients will continue to receive mavacamten.
The primary endpoint is the composite of the number of patients who decide to proceed with SRT prior to or at week 16 and the number of patients who remain guideline eligible for SRT at week 16 in the mavacamten group vs the placebo group.
Findings from the placebo-controlled period demonstrate that the trial met its primary endpoint at week 16, indicating a greater reduction in the number of SRT procedures performed in the mavacamten arm vs the placebo arm. The safety profile of mavacamten was consistent with that seen in previous studies.
“We are encouraged by the findings from this important study, which add to the growing body of clinical evidence that supports the promise of mavacamten for patients living with obstructive HCM,” said Roland Chen, MD, Senior Vice President, Cardiovascular Development at Bristol Myers Squibb. “We look forward to sharing the results from VALOR-HCM at the American College of Cardiology 71st Annual Scientific Session & Expo taking place in April.”
The Food and Drug Administration (FDA) is currently reviewing the New Drug Application for mavacamten for the treatment of patients with symptomatic obstructive HCM. The submission is based on data from the phase 3 EXPLORER-HCM trial (ClinicalTrials.gov: NCT03470545). A Prescription Drug User Fee Act (PDUFA) target date of April 28, 2022 has been set for the application. Study data from VALOR-HCM will also be submitted to the Agency for review.
Bristol Myers Squibb announces positive topline results from phase 3 VALOR-HCM trial, evaluating mavacamten in patients with obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy. News release. Bristol Myers Squibb. Accessed February 16, 2022. https://www.businesswire.com/news/home/20220215005925/en/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-from-Phase-3-VALOR-HCM-Trial-Evaluating-Mavacamten-in-Patients-with-Obstructive-Hypertrophic-Cardiomyopathy-Who-are-Eligible-for-Septal-Reduction-Therapy