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Study Finds Mavacamten Effective at Reducing Need for Surgical oHCM Interventions


Data underscored the efficacy of mavacamten in reducing eligibility for surgical intervention among patients with obstructive hypertrophic cardiomyopathy (oHCM).

New research presented at the American College of Cardiology (ACC)’s 71st Scientific Session highlighted the efficacy of mavacamten in reducing the need for surgical intervention among patients with obstructive hypertrophic cardiomyopathy (oHCM).

Results of the VALOR-HCM study were presented by Milind Desai, MD, MBA, director of the Hypertrophic Cardiomyopathy Center and director of clinical operations at Cleveland Clinic’s Heart Vascular and Thoracic Institute.

Due to left ventricular outflow tract obstruction (LVOTO), HCM can lead to severe symptoms and exercise intolerance. Affecting between 15 million and 20 million people worldwide, HCM is the most common genetic heart condition—although most patients are unaware they have it. The condition is also a major driver of health care costs and utilization as it is associated with increased risks of atrial fibrillation, stroke, and heart failure.

Although there are currently no medical therapies developed specifically for HCM, eligible patients can undergo septal reduction therapies (SRT), either performed through surgery or via alcohol ablation.

In an effort to identify noninvasive alternatives to SRT for this patient population, researchers carried out the multicenter phase 3 VALOR-HCM trial. All participants were 18 years or older, had symptomatic oHCM, and met 2011 ACC/American Heart Association HCM-guideline criteria.

Participants were also on maximally tolerated medical therapy at the time of inclusion and recruited from 19 different health centers.

Mavacamten is a β-cardiac myosin inhibitor that has been shown to reduce LVOT and lead to improvement in symptoms, exercise capacity, and quality of life.

After receiving the treatment or placebo for 16 weeks, patients’ composite SRT guideline eligibility or decision to complete SRT were assessed. At any time throughout the trial, patients could choose to proceed with SRT.

Of the 112 patients enrolled (56 of whom received mavacamten 2.5, 5, 10, or 15 mg QD), their mean age was 60 years, and 89% were White. During his presentation, Desai stressed the fact that 50% of participants were women. Ninety-two percent of patients had New York Heart Association (NYHA) class III oHCM; all had a documented LV ejection fraction of at least 60%.

After 16 weeks, a total of 10 patients in the mavacamten arm decided to proceed with SRT or were eligible to do so, compared with 43 in the placebo arm, resulting in a treatment difference of 58.93 (95% CI, 43.99-73.87; P <.0001). In other words, 18% of patients receiving the mavacamten were eligible for SRT after 16 weeks vs 76.8% of placebo recipients.

Two patients in each arm went through with SRT by week 16, with 8 in the intervention cohort and 39 in the control group eligible and opting not to complete SRT. SRT status was not evaluable for 2 patients in the control group.

In addition, those who received mavacamten exhibited a reduction in postexercise LVOT gradient, at least 1 class improvement in NYHA Class, improvement in Kansas City Cardiomyopathy Questionaire clinical summary score, reduction in N-terminal-prohormone BNP, and reduction in troponin I (all P < .0001).

The data were also the first to show mavacamten’s concomitant use with disopyramide.

No new safety signals were detected, although 2 patients in the mavacamten group experienced a drop in ejection fraction by more than 50%, had to stop the drug until recovery, and were able to restart at a lower dose. Overall, “this was very well tolerated,” Desai said, adding that “long-term safety needs to be ascertained” for this first-in-class treatment.

“Everyone should be offered background therapy before you offer an intervention,” Desai said.

During the panel discussion, experts brought up concerns regarding patients’ titration schedules and the relatively short follow-up period. In comparison, the EXPLORER-HCM study was conducted over a period of 30 weeks as opposed to 16.

Additional research is warranted to better understand durability of improvement beyond 16 weeks, while, as with any new introduction of medication or technology, “there has to be the appropriate amount of trepidation,” Desai said. The FDA is expected to issue a decision on mavacamten for HCM by the end of April 2022.

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