Mavacamten May Improve Health Status in Patients with Obstructive HCM

May 15, 2021
Jonathan Alicea

Improvements in patient symptoms, function, and quality of life were not sustained once treatment was discontinued.

Mavacamten, a first-in-class cardiac myosin inhibitor, was associated with substantial improvements in the health status of patients with obstructive hypertrophic myocardiopathy (oHCM), according to findings presented at the American College of Cardiology (ACC) Annual Scientific Session.

HCM is characterized by unexplained left ventricular hypertrophy. Investigative drug mavacamten is a targeted inhibitor that decreases contractile function as well as improves VO2. Nevertheless, little has been understood about the drug’s effect on patient symptoms, function, and quality of life.

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In the pivotal phase 3 EXPLORER-HCM trial, patients (n = 251) with left ventricular outflow tract (LVOT) ≥50 mmHg and New York Heart Association (NYHA) class II-III symptoms were enrolled. They were then randomized 1:1 to either mavacamten or placebo for 30 weeks.

Health status was evaluated according to the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OSS) at weeks 6, 12, 18, 30, and 38. The disease-specific questionnaire consisted of 23 items and quantified symptoms, physical function, social function, and quality of life, with higher scores (0-100) representing fewer symptoms, better function, and better quality of life, respectively.

The investigative team then analyzed change from baseline in KCCQ score using mixed model repeated measures and responder analyses. 

The findings for this analysis were presented at the conference by John Spertus, MD, of Univeristy of Missouri-Kansas City.

Of the 123 patients in the mavacamten cohort, 92 complete the KCCQ; of the 128 patients in the placebo cohort, 88 completed the questionnaire. The mean age of the KCCQ population was 58 years, and the majority (61%) was male, white (92%), and NYHA class II at baseline (73%).

Spertus and colleagues thus observed early and sustained improvements in KCCQ in the mavacamten group through week 30 compared to the placebo group (mean difference, +9.1; 95% CI, 5.5-12.8). They noted in particular that the mean difference in score was among the largest for any medication. However, these improvements were not sustained through week 38 (post-treatment).

Furthermore, the investigators reported that, at week 30, a greater proportion (36%) of patients who received mavacamten achieved a very large clinically meaningful improvement in KCCQ — defined as ≥20-points—when compared with the placebo group (15%).

In fact, a higher proportion of placebo patients experienced no change (32%) or a deterioration (23%) in their health status compared with mavacamten patients (20% and 32%, respectively).

In an interview with HCPLive®, Spertus indicated that more work needs to be done to fully understand the mechanisms behind these observed improvements in patients.

“As we learn what’s causing these quality of life benefits, there may be other diseases that may also benefit from the drug,” he noted. As an example, he pointed to the potential for the drug in patients with heart failure and a reduced ejection fraction.

Even then, studies assessing patients not necessarily with hemodynamically significant oHCM—as well as longer-term trials—are warranted.

The study, “Health Status Benefits of Mavacamten in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results from the EXPLORER-HCM Randomized Clinical Trial,” was presented at ACC 2021.


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