In pivotal trial, mavacamten is first drug to show functional benefit in HCM

A hallmark of obstructive hypertrophic cardiomyopathy is the lack of effective pharmacologic therapy, but that may soon change as there is now evidence that an investigational cardiac myosin inhibitor improves not only the symptoms of cardiomyopathy but also — and this is a first — improves heart function.

The drug, which is a first in class, is mavacamten, and the impressive findings come from EXPLORER-HCM, which was reported in a Hot Line presentation at the European Society of Cardiology ESC 2020 The Digital Experience.

“The results of this pivotal trial support a role for disease-specific therapy for obstructive hypertrophic cardiomyopathy (HCM) which treats the cause instead of just managing symptoms,” said principal investigator Iacopo Olivotto, MD, of Careggi University Hospital, Florence, Italy.

The results of the study were also published in The Lancet.

EXPLORER-HCM was a pivotal, global, phase III, randomized, placebo-controlled clinical trial that tested the efficacy and safety of mavacamten in treating symptomatic obstructive HCM. A total of 251 patients received once daily mavacamten or placebo for 30 weeks.

“The primary endpoint assessed the treatment effect of mavacamten at week 30 relative to placebo on both symptoms and cardiac function,” Olivotto said. “It was defined as achieving ≥1.5 mL/kg/min improvement in peak oxygen consumption (peak VO2) and ≥1 New York Heart Association (NYHA) class reduction OR 2) ≥3.0 mL/kg/min improvement in peak VO2 and no worsening of NYHA class.”

“Secondary endpoints included change from baseline to week 30 in post-exercise LVOT gradient and patient reported outcomes such as the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQCSS) and HCM Symptom Questionnaire-Shortness-of-Breath (HCMSQ-SoB) subscore,” the study authors wrote.

Among the findings:

  • 36.6% patients on mavacamten met the primary composite endpoint versus 22 (17.2%) on placebo (P=0.0005).
  • All secondary endpoints, including post-exercise LVOT gradient and patient-reported outcomes, also demonstrated statistically significant improvements for mavacamten as compared to placebo (P<0.0006 for all).
  • Eleven serious adverse events were reported in 8.1% of patients on mavacamten versus 20 events in 8.6% of patients on placebo.

Olivotto noted that the study excluded patients on disopyramide and patients with severe (NYHA class IV) symptoms, both of which may limit the ability to generalize the findings. Also, the study enrolled few young patients or non-white patients.

He concluded, “in this first positive randomized phase 3 trial in patients with obstructive hypertrophic cardiomyopathy, mavacamten treatment improved functional capacity, LVOT gradient, symptoms, and key aspects of health status.” The results of this pivotal trial highlight the benefits of disease-specific treatment in hypertrophic cardiomyopathy.

Peggy Peck, Editor-in-Chief, BreakingMED™

Cat ID: 204

Topic ID: 74,204,204,308,5,914,192,925,203