Mavacamten Shows Promise as Long-Term Treatment for HCM in MAVA-LTE Trial

Florian Rader, MD

Right on the heels of positive results from the VALOR-HCM trial, mavacamten is continuing to grab headlines at the American College of Cardiology’s 71st Scientific Sessions with data from the MAVA-LTE trial.

An ongoing, dose-blinded, 5-year extension study that includes 231 of the 244 patients from the EXPLORER-HCM trial, results from MAVA-LTE presented at ACC.22 demonstrated mavacamten use was associated with clinically important improvements in LVOT gradients, NYHA class, and NT-proBNP levels at and beyond 48 weeks in patients with symptomatic obstructive hypertrophic cardiomyopathy, with no new safety signals observed.

“These data are very consistent with the initial trial results—obstruction in the heart was relieved, two-thirds of patients felt better, and disease severity improved,” said lead investigator Florian Rader, MD, co-director of the Hypertrophic Cardiology Clinic at Cedars Sinai, who added that EXPLORER-LTE is the largest and longest report of mavacamten treatment in obstructive HCM, in a statement. “The thickening caused by HCM can obstruct blood flow out of the heart, which results in burdensome symptoms and poor quality of life for many patients. Based on these results, the drug doesn’t lose its effectiveness over time and appears to be safe and well tolerated long term.”

MAVA-LTE was designed with the intent of providing more data from a long-term perspective related to the effects of mavacamten on than the phase 3 EXPLORER-HCM trial. As such, the ongoing trial enrolled 231 of the 244 participants who completed EXPLORER-HCM.

Patients included in the trial could receive 2.5, 5, 10, or 15 mg of mavacamten daily, with adjustments occurring, as needed, at weeks 4, 8, 12, and 24 based on results of echocardiograms, which assessed the degree of obstruction by gradient and assessed ejection fraction. As part of study protocol, if the gradient was above 30 mmHg, patients were eligible to increase the dose and, if signs of reduced left ventricular ejection fraction were observed clinicians were advised to lower the dose or temporarily stop the medication. Investigators noted the majority of patients received10 mg or less, with 83% and 85% of patients receiving 10 mg or less at weeks 48 and 84, respectively. Investigators pointed out the analysis presented at ACC.22 represents an interim analysis, with 206 patients with data out to 48 weeks and 66 patients with data out to 84 weeks.

At the time of data cutoff for the ACC analysis, 231 patients were included in the analysis. This cohort had a mean age of 60 years, 39% were female, and the median time enrolled in the study was 62.3 (range, 0.3-123.9 weeks). From this cohort, investigators obtained data related to 317 patient-years of exposure for inclusion in their analysis.

In their analyses, results indicated use of mavacamten was associated with improvements in LVOT gradients, NT-proBNP, and NYHA class from baseline to 48 weeks. Investigators highlighted changes in NYHA class at 48 weeks, with 67.5% of patients improving by at least 1 class, 7.3% improving by 2 or more classes, and just 1.5% experiencing a regression of 1 class or more, with 31.1% experiencing no change.

“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,” Rader added. “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.”

This study, “Updated cumulative results of treatment with mavacamten from the EXPLORER-LTE cohort of the MAVA-LTE study in patients with obstructive hypertrophic cardiomyopathy,” was presented at ACC.22