American College of Cardiology

American College of Cardiology

Source:

Spertus JA, et al. Featured Clinical Rearch 1. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).

Disclosures: The EXPLORER-HCM study was funded by MyoKardia, a Bristol Myers Squibb company. Spertus reports he received consultant fees from MyoKardia, owns the copyright to the Kansas City Cardiomyopathy Questionnaire, and has served as a consultant to Amgen, Bayer, Janssen, Novartis and UnitedHealthcare. He also serves on the board of directors for Blue Cross Blue Shield of Kansas. Please see the study for all other authors’ relevant financial disclosures.
May 15, 2021
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Marked health status improvement with mavacamten in obstructive hypertrophic cardiomyopathy

Source:

Spertus JA, et al. Featured Clinical Rearch 1. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).

Disclosures: The EXPLORER-HCM study was funded by MyoKardia, a Bristol Myers Squibb company. Spertus reports he received consultant fees from MyoKardia, owns the copyright to the Kansas City Cardiomyopathy Questionnaire, and has served as a consultant to Amgen, Bayer, Janssen, Novartis and UnitedHealthcare. He also serves on the board of directors for Blue Cross Blue Shield of Kansas. Please see the study for all other authors’ relevant financial disclosures.
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The cardiac myosin inhibitor mavacamten substantially improved health status in patients with symptomatic obstructive hypertrophic cardiomyopathy, with benefits observed early after treatment, according to new data from EXPLORER-HCM.

John A. Spertus

Presenting new health status data from the trial at the American College of Cardiology Scientific Session, John A. Spertus, MD, MPH, the Lauer/Missouri Endowed Chair and professor at University of Missouri Kansas City and Saint Luke’s Mid America Heart Institute, said mean Kansas City Cardiomyopathy Questionnaire overall summary score differences favoring mavacamten (MyoKadria) were amongst the largest he has observed for any medication, eclipsed only by structural heart interventions.

Heart with gears
Source: Adobe Stock

“There is a very impressive improvement in the symptoms, function and quality of life of [mavacamten]-treated patients and it is really impressive that, when on the medicine, patients get the benefit; when they come off the medicine, benefit goes away,” Spertus told Healio. “It supports a direct cause-and-effect relationship between treatment and improved health status.”

New health status data

As Healio previously reported, treatment with mavacamten, a novel oral allosteric modulator of cardiac myosin, was shown to significantly improve symptoms, quality of life and functional status compared with placebo among participants with symptomatic, obstructive hypertrophic cardiomyopathy. Initial data were presented at the European Society of Cardiology Congress in August 2020.

For the secondary analysis, Spertus and colleagues analyzed data from 251 adults with symptomatic obstructive hypertrophic cardiomyopathy (left ventricular outflow tract gradient 50 mm Hg and New York Heart Association class II–III) who were randomly assigned mavacamten (n = 123) or placebo (n = 88) for 30 weeks, followed by an 8-week washout period. The primary outcome was KCCQ scores, administered at baseline and again at 6, 12, 18, and 30 weeks (end of treatment), as well as at 38 weeks (end of study). Within the cohort, 69% completed the KCCQ at baseline and week 30.

At 30 weeks, change in KCCQ-OS score was a mean 9.1 points greater for participants who received mavacamten vs. placebo (mean score, 14.9 vs. 5.4; 95% CI, 5.5–12.8; P < .0001), with similar benefits observed across all KCCQ subscales. The proportion of patients with a very large change, defined as at least 20 points on the KCCQ scale, was 36% in the mavacamten group vs. 15% in the placebo group, with an estimated absolute difference of 21% (95% CI, 8.8–33.4) and number needed to treat of just five, he said during the presentation.

The observed gains immediately returned to baseline after treatment was stopped and symptoms were no different than placebo-treated patients, Spertus said.

“The magnitude of benefit was surprising,” Spertus told Healio. “It left me wanting to understand: Why? Is it the reduction in the gradient? Is it the change in diastolic function? What is it about the physiology that led to such an impressive improvement in health status? We do not often see this. It is far more important that you alter a patient’s health status than you alter some surrogate biomarker.”

The results were simultaneously published in The Lancet.

Identifying responders

Understanding the clinical importance of a 9.1-point difference in KCCQ scores is difficult, Spertus said, as not all trial participants respond to treatment the same way. He cited several study limitations, including some missing data due to administrative errors with the app used to collect information. He said additional study is needed to determine whether comparable benefits would be seen in patients with less impairment.

Spertus said it is important to identify the responders who will benefit from treatment the most.

“Ultimately, this is a reversal drug, so a clinician can try it and, if the patient responds, you keep going,” Spertus said. “But it is still interesting to figure out [the best responders] to identify new strategies down the road.”

In July, the FDA granted a breakthrough therapy designation to mavacamten for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy.

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