Mavacamten Can Reduce Need for Surgery in Hypertrophic Cardiomyopathy

Milind Desai, MD, MBA

Data from the VALOR-HCM trial indicate use of mavacamten significantly reduced the need for surgical intervention among patients with symptomatic hypertrophic cardiomyopathy (HCM).

Presented at the American College of Cardiology’s 71s Annual Scientific Session, results of the phase 3 trial indicate use of mavacamten was associated with severely symptomatic drug-refractory obstructive hypertrophic cardiomyopathy patients eligible for septal reduction therapy (SRT), with just 17.9% of patients on mavacamtenstill eligible for SRT at the end of the study period compared with 76.8% of those on placebo.

“These were very symptomatic, sick patients who were on maximally tolerated medical therapy and were faced with the decision of whether or not to have septal reduction therapy to relieve the obstruction. In taking this drug, they got a whole lot better across the board,” said lead investigator Milind Y. Desai, MD, MBA, director of the Hypertrophic Cardiomyopathy Center, director of clinical operations in Cleveland Clinic’s Heart Vascular and Thoracic Institute, who presented the findings at ACC.22. “This is really the first pharmacotherapy that offers a viable medical option for people with obstructive HCM short of needing a procedure.”

With a lack of approved medical therapies and SRT requiring specialized care that is often unavailable for some patients, a significant unmet need exists for noninvasive alternatives as a treatment for patients with highly symptomatic obstructive HCM. With this in mind, VALOR-HCM was created with the intent of assessing whether the selective cardiac myosin inhibitor mavacamten might allow these patients to improve sufficiently to the point they long meet guideline criteria for SRT or chose not to undergo SRT for 16 weeks.

A phase 3, double-blind, placebo-controlled trial, VALOR-HCM enrolled patients with symptomatic HCM aged 18 years and older who met the 2011 ACC/AHA HCM-guideline criteria and were willing to undergo SRT from 19 HCM centers in the US. A total of 112 patients underwent randomization in a 1:1 ratio to receive mavacamten, in either 2.5, 5, 10, or 15 mg once a day, or placebo therapy for 16 weeks. The study cohort had a mean age of 60 years, 49% were women, 89% were White, and 92% met criteria for NYHA class 3 heart failure.

As part of study protocol, participants underwent clinical exams and echocardiograms at baseline, once monthly and at the conclusion of the 16-week treatment period. The primary outcome of interest was the proportion of patients still considered eligible for or electing to receive SRT. Secondary outcomes of interest for the study included changes in post-exercise LVOT, proportion of patients with improvement in NYHA Class, and changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores.

At the end of the 16-week treatment period, 76.8% of those randomized to placebo and 17.6% of those randomized to mavacamten were found to meet guideline criteria for SRT (Treatment difference: 58.93 [95% CI, 43.99-73.87]; P <.0001). Analysis of secondary results indicated patients randomized to mavacamten experienced a reduction in resting LVOT gradient (Difference: -33.4 mmHg [95% CI, -42.3 to -24.5]), greater improvements in NYHA class, and a greater change in KCCQ-23 clinical summary score (Difference: 9.4 mmHg [95% CI, 4.9-14.0]) than those randomized to placebo. Regarding NYHA class improvement, 63% of patients receiving mavacamten improved at least 1 class and 27% improved 2 or more classes compared to the 21% of those receiving placebo who improved 1 class or more and 2% who improved 2 classes or more.

“This is a big win for patients, especially as many people don’t want surgery, are at high risk for complications or don’t have good anatomy for ablation,” Desai said. “We are hoping this study will also draw much-needed attention to HCM. This disease is woefully underrecognized. There are not enough HCM experts and not enough proven medical therapies, so there are many opportunities to do better.”

This study, “Myosin Inhibition to Defer Surgical Myectomy or Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy,” was presented at ACC.22.