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Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results From
Milind Y Desai1,2,3, Kathy Wolski2,3, Anjali Owens4
1Hypertrophic Cardiomyopathy Center (M.Y.D., N.G.S.), Cleveland Clinic, OH.
Insights
Mavacamten significantly reduced the need for septal reduction therapy (SRT) in obstructive hypertrophic cardiomyopathy (HCM) patients over 128 weeks. Most patients remained on long-term mavacamten, showing sustained symptom improvement and reduced obstruction.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Obstructive hypertrophic cardiomyopathy (HCM) is a severe condition requiring treatment for symptomatic patients.
- Septal reduction therapy (SRT) is an option for patients with obstructive HCM.
- Mavacamten has shown short-term efficacy in reducing the need for SRT in obstructive HCM.
Purpose of the Study:
- To evaluate the longer-term effects of mavacamten in patients with obstructive HCM.
- To assess the proportion of patients who avoided SRT at 128 weeks.
- To determine the safety and efficacy of long-term mavacamten treatment.
Main Methods:
- A double-blind, randomized, placebo-controlled trial (VALOR-HCM) involving symptomatic obstructive HCM patients eligible for SRT.
- Patients received mavacamten or placebo for up to 128 weeks, with dose titration based on echocardiographic parameters.
- The primary endpoint was the proportion of patients proceeding with SRT or remaining guideline-eligible at week 128.
Main Results:
- At 128 weeks, 15.7% of patients met the composite endpoint (underwent SRT, were SRT-eligible, or SRT-status unevaluable).
- 80.5% of patients showed at least one New York Heart Association class improvement, with sustained reduction in left ventricular outflow tract gradients.
- 13.8% of patients experienced left ventricular ejection fraction <50%, and 10.2% developed new-onset atrial fibrillation.
Conclusions:
- Long-term mavacamten treatment in obstructive HCM patients resulted in sustained freedom from SRT at 128 weeks.
- Nearly 90% of patients remained on mavacamten, demonstrating sustained clinical benefit.
- Mavacamten offers a promising long-term therapeutic option for severely symptomatic obstructive HCM.
Background:
In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128.
Methods:
A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128.
Results:
At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years).
Conclusions:
In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.
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