Patients Taking Mavacamten Report Big Leaps in Quality of Life

The investigational drug for obstructive hypertrophic cardiomyopathy is in front of FDA, with an approval target date of January 28, 2022.

Patients with an inherited, debilitating heart condition reported major improvements in quality of life while taking mavacamten, an investigational therapy now being evaluated by FDA, according to results presented today during the 70th American College of Cardiology Scientific Session.

Results were simultaneously reported in the Lancet.1

If approved, mavacamten would be the first treatment to deal directly with the mechanism behind obstructive hypertrophic cardiomyopathy (HCM), which causes the heart muscle to contract far more than normal and thicken, causing dangerous symptoms and sometimes sudden death. For decades, clinicians have only been able to treat patients’ symptoms—using drugs developed to treat other heart problems—with limited effectiveness. Patients with obstructive HCM live with physical limitations and fatigue, and many undergo surgery to relieve the heart muscle thickening as their disease progresses.

Mavacamten, a targeted inhibitor of cardiac myosin, works to reduce the hypercontractility, which is often caused by genetic variants that put the heart into overdrive. By acting on the mechanism of HCM, this novel treatment not only slows the progression of the disease but also helps some patients improve.

The main phase 3 results from EXPLORER-HCM, presented in August 2020 during the European Society of Cardiology virtual meeting, met all primary and secondary end points and showed significant improvements in multiple measures of patients’ symptoms and cardiac function. double-blind, placebo-controlled trial, patients with symptomatic obstructive HCM (LVOT gradient ≥50 mmHg and NYHA Class II-III) were randomized 1:1 to receive mavacamten (n=123) or placebo (n=128) for 30 weeks, followed by an 8-week washout period.

Today, investigator John Spertus, MD, MPH, of the University of Missouri-Kansas City and Saint Luke’s MidAmerica Heart Institute, presented results from the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ is a well-known, frequently used study tool that grades rates patients’ quality of life responses on a scale of 0 to 100, with higher scores indicating better quality of life. When scores improve by less than 5 points, a patient’s condition is considered unchanged; a gain between 5 and 10 points is considered a small improvement; 10 to 20 points is considered a moderate improvement, and a 20-point gain is considered a large improvement. The KCCQ was administered at baseline and at weeks 6, 12, 18, 30 and 38.

Results for the EXPLORER-HCM patients showed:

  • The average score for patients taking mavacamten rose quickly and was 9.1 points higher than the placebo group by the end of the 30-week treatment period.
  • Scales that focused on symptoms and physical limits showed that patients who took mavacamten did not maintain progress after treatment ended.
  • Among 19 clinical trials that have reported mean KCCQ differences between a study drug or intervention and placebo, results for EXPLORER-HCM rank in the top third. Spertus said of mavacamten, "It's really only eclipsed by the structural heart interventions."
  • 36% of patients taking mavacamten reported improvements at least 20 points higher, compared with 15% taking placebo. By contrast, 9% of those taking mavacamten reported a declining score, compared with 23% taking placebo.
  • A key limitation that investigators reported in their findings: 28% of patients were missing data at baseline or in the follow-up. Spertus said during the session that this was largely due to administrative reasons, and researchers conducted "extensive analyses of the missing data" and there were no observable biases.

“This new analysis of the EXPLORER-HCM data provides important insights into the benefits myosin inhibition can have in improving the health status of patients with severe obstructive hypertrophic cardiomyopathy," Spertus said in a statement.

In the Lancet article, investigators wrote that one finding stands out: “In particular, the proportion of patients with very large (≥ 20 points) improvements in their KCCQ-[Overall Summary] score was much greater than that of patients randomly assigned to placebo, suggesting that for every 5 patients treated, 1 will feel substantially better."

The study authors contrasted the effects of mavacamten on patients with obstructive HCM with that of tafamidis, “the only other medical therapy approved in the past few years with such a large benefit in KCCQ scores,” for patients with amyloid heart disease. While tafamidis “sustained health status” in contrast with the decline seen in patients taking placebo, the authors observed that mavacamten brought about improvement in health, followed by “the unprecedented complete reversal of KCCQ improvements observed 8 weeks after treatment withdrawal.” The authors noted that this suggested treatment will have to be ongoing.

Spertus pointed out this phenomeon during his presentation. "What's particularly unique about this study design, and using a drug that appears to directly impact the underlying pathophysiology of the disease is we can see what happened after the drug was withdrawn." he said, pointing to the graph where the curve immediately fell below the line for the placebo arm as the effects of mavacamten dissipated.

When treatment was withdrawn, "The health status of the mavacamten-treated patients returned right to baseline and was no different than the placebo treated patients."

After the EXPLORER-HCM results were announced last year, drug sponsor MyoKardia was acquired by Bristol Myers Squibb (BMS) for $13.1 billion, and in March 2021 the FDA accepted the BMS application, setting a goal date for approval of January 28, 2022, under the Prescription Drug User Fee Act (PDUFA).


1. Spertus JA. Fine JT, Elliott P, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online May 15, 2021. doi:10.1016/ S0140-6736(21)00763-7

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