Mavacamten Use Can Reduce Need for Septal Reduction Therapy in oHCM


Results of the 56-week VALOR-HCM trial provide new insight into the effects of mavacamten in patients with highly symptomatic obstructive hypertrophic cardiomyopathy referred for septal reduction therapy.

Milind Desai, MD | Credit: Twitter

Milind Desai, MD
Credit: Twitter

Data from VALOR-HCM LTE suggest use of the cardiac myosin inhibitor mavacamten (Camzyos) could reduce the need for septal reduction therapy (SRT) among patients with obstructive hypertrophic cardiomyopathy (HCM).

Results of the study, which were presented at the European Society of Cardiology (ESC) Congress 2023, indicate the rate of SRT or SRT eligibility in the placebo-crossover group was more than twice that of the mavacamten only arm, with use of mavacamten also associated with improvements in resting and Valsalva left ventricular outflow tract (LVOT) gradients.1

“The 56-week late-breaking analysis of VALOR-HCM LTE builds upon previous findings and demonstrates the consistent impact of this oral treatment for severely symptomatic obstructive HCM patients by showing that nearly 9 out of 10 patients treated with this drug have continued in this long-term extension trial without SRT at either 40 or 56 weeks of treatment,” said Milind Desai, MD, MBA, director, center for hypertrophic cardiomyopathy and vice chair of education in the Heart, Vascular & Thoracic Institute at Cleveland Clinic.2 “These findings are important for our continued understanding of this treatment and encouraging for patients hoping for non-surgical options.”

A double-blind, placebo-controlled, randomized clinical trial with a placebo crossover at 16, VALOR-HCM was designed to assess the efficacy and safety of mavacamten in patients with sympatomatic obstructive HCM referred for SRT. Conducted from July 2020 to November 2022 in 19 HCM centers in the US, the trial enrolled 112 patients with highly symptomatic obstructive HCM. Of these 108 were considered eligible for the 56-week evaluation.1

The primary endpoint of interest for the trial was the proportion of patients undergoing SRT, remaining guideline-eligible, or unevaluable SRT status at week 56. For inclusion in the trial, patients needed to be taking maximally tolerated medical therapy and referred for consideration of SRT, based on 2011 American College of Cardiology/American Heart Association guidelines. Additional inclusion criteria required patients to be at least 18 years or older and have severe dyspnea or chest pain.1

Upon analysis, 8.9% of patients in the original mavacamten group and 19.2% of patients in the placebo crossover group met the composite endpoint. Among the original mavacamten group, 3 underwent SRT, 1 was SRT eligible, and 1 was not SRT evaluable. Among the placebo crossover group, 3 underwent SRT, 4 were SRT eligible, and 3 were not SRT evaluable. Overall, 96 of 108 patients continued mavacamten long term.1

Further analysis indicated there were sustained reductions in resting (mean difference, −34.0 mmHg; 95% Confidence Interval [CI], −43.5 to −24.5 mmHg and −33.2mmHg; 95%CI, −41.9 to −24.5 mmHg) and Valsalva (mean difference, −45.6 mmHg; 95% CI, −56.5 to −34.6 mmHg and −54.6mmHg; 95% CI, −66.0 to −43.3 mmHg) LVOT gradients between the mavacamten and placebo-to-mavacamten groups, respectively, after 56 weeks. Investigators also pointed out there was an improvement in NYHA class of 1 or more in 93% of the original mavacamten group and 73% of the placebo crossover group.1

When assessing safety outcomes, investigators found 12 of 108 patients (11.1%; 95% CI, 5.87%-18.60%), including 12.5% in the original mavacamten group and 9.6% in the placebo crossover group, had an LVEF less than 50%. Of these, 2 had an LVEF equal to or less than 30%, 1 died, and 9 continued treatment.1

“The new long-term data presented at ESC were consistent with the primary analyses from each study, further underscoring the benefit our first-in-class therapy can provide to patients with symptomatic obstructive HCM,” said Amy Sehnert, MD, vice president and head of Cardiomyopathy and Heart Failure Clinical Development at Bristol Myers Squibb.2

In an Editor’s Note written by Sharlene M. Day, MD, James E. Udelson, MD, Robert O. Bonow, MD, MS, all of whom are editorial members of JAMA Cardiology, celebrated the results of the study and their implications for patients with obstructive HCM, but also pointed out the apparent risk for decrease in left ventricular ejection fraction observed in clinical trials of mavacamten.3

“This safety signal of potential left ventricular dysfunction highlights the need for conservative drug titration and continued, vigilant echocardiographic surveillance in patients treated with cardiac myosin inhibitors, as specified by the FDA Risk Evaluation and Mitigation Strategy program,” wrote the trio.3


  1. Desai MY, Owens A, Wolski K, et al. Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial. JAMA Cardiol. Published online August 28, 2023. doi:10.1001/jamacardio.2023.3342
  2. Bristol Myers Squibb. Long-term follow-up data from two phase 3 studies of CAMZYOS® (mavacamten) demonstrate consistent and durable response in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). News. August 28, 2023. Accessed August 28, 2023.
  3. Day SM, Udelson JE, Bonow RO. Long-Term Efficacy and Safety of Mavacamten in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. JAMA Cardiol. Published online August 28, 2023. doi:10.1001/jamacardio.2023.3357
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