Efficacy, Safety of Mavacamten in Treating Obstructive HCM Holds Up in EXPLORER-LTE Cohort of MAVA-LTE Study

Use of mavacamten to treat symptomatic obstructive hypertrophic cardiomyopathy (HCM) resulted in continued benefits in patient quality of life and outcomes over an extended period of time, according to interim data from the EXPLORER-LTE cohort of the MAVA-LTE extension study presented April 3 at ACC.22. Specifically, researchers said mavacamten was associated with significant and sustained improvements in left ventricular outflow tract (LVOT) gradients.

MAVA-LTE is an ongoing, dose-blinded five-year extension study that includes 231 of 244 patients who completed treatment in the phase 3 EXPLORER-HCM trial. Results from EXPLORER-HCM showed significant improvements in patients' health status, symptoms, exercise capacity and quality of life among those taking mavacamten compared with placebo after 30 weeks. The MAVA-LTE study was designed to collect longer-term data. At data cutoff for this analysis, patients were 60 years old on average and 39% were female.

Patients initially were provided 5 mg of once daily mavacamten after stopping the drug, but could ultimately take 2.5, 5, 10 or 15 mg, with dose adjustments at weeks four, eight and 12 and again at 24 weeks based on local site read echocardiograms, which looked at the degree of obstruction by gradient and checked for normal ejection fraction (>50%). If the gradient was above 30 mmHg, patients were eligible to increase the dose to further reduce the gradient and obstruction. If patients showed signs of reduced left ventricular ejection fraction (<50%), treating clinicians were advised to lower the dose or temporarily stop the medication.

Overall results found most patients were on 5 or 10 mg, with only 15% on the 15 mg dose. The median follow-up was 62 weeks and ranged from one to 124 weeks, signifying that not all patients had been taking mavacamten at the designated 48- or 84-week follow-up, which are reported in this interim analysis. In patients who were assessed at these time points, 206 at 48 weeks and 66 at 84 weeks, the degree of obstruction measured by LVOT gradient was lowered on average by 36 mmHg at 48 weeks (a 74% reduction from baseline); this reduction was sustained through week 84. At week 84, 83.5% of patients who had follow-up at that time point had LVOT gradients less than 30 mmHg.

In terms of NYHA class, 68% of patients improved by at least one class designation, with the most dramatic change in Class I, with the percentage of patients at Class 1 jumping from only 6% at baseline, to 55% by week 48. In contrast, 29% of patients were in Class III, showing noticeable limitation with physical activity at the start of the study. The proportion of people in this class dropped to 4.9% at 48 weeks, researchers said.

At baseline, 94% of patients had some degree of shortness of breath with exercise compared with only 45% at 48 weeks. In addition, the heart failure marker NTproBNP decreased by 480 ng/L at week 48 and 488 ng/L at week 84 – a 63% reduction. Mavacamten was also well tolerated with no new or unexpected adverse events reported.

"There have been limited medication options for HCM and many patients end up having to go through surgical removal of a portion of the thickened heart muscle or undergo alcohol septal ablation to reduce the obstruction. Although these invasive treatment options are effective, they also have risks," said Florian Rader, MD, FACC, the study's lead author. "Mavacamten is the first medication specifically designed to relieve this obstruction and as the data shows, it helps patients feel better, and they are able to live a more active life. If this medication continues to be effective over time, it may also help keep patients from having to undergo an invasive procedure or open-heart surgery to relieve the obstruction."

Mavacamten is currently under review with the U.S. Food and Drug Administration for use in obstructive HCM, with a decision expected at the end of April 2022.

Clinical Topics: Heart Failure and Cardiomyopathies, Statins

Keywords: ACC Annual Scientific Session, ACC22, Cardiomyopathy, Hypertrophic, Benzylamines, Uracil

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