Mavacamten’s Improvements in oHCM Symptoms Sustained in Long-Term Extension

Mavacamten treatment led to rapid and sustained improvements in obstructive hypertrophic cardiomyopathy (oHCM) for ≤5 years, according to a long-term extension of the EXPLORER-HCM study.1

Presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Anjali Owens, MD, a cardiovascular fellow at the Hospital of the University of Pennsylvania, the study investigated the EXPLORER-LTE cohort, the longest and largest evaluation of oHCM patients treated with mavacamten.1,2

“We treat patients with this disease, and we know that it’s dynamic. There are good days, there are bad days, and ideally what we want for our patients is for them to be able to live without thinking about their disease,” Owens told HCPLive in an exclusive interview. “This drug gives us the ability to have way more good days than bad days, and over a 5-year period, this makes a huge difference in quality of life.”

EXPLORER-HCM and -LTE

The original EXPLORER-HCM trial enrolled 251 patients, who were randomly assigned to either mavacamten (n = 123) or placebo (n = 128). Of these patients, 45 mavacamten recipients and 22 placebo recipients met the primary endpoint of increases in peak oxygen consumption and ≥1 New York Heart Association (NYHA) class reduction. Additionally, mavacamten recipients saw greater reductions in left ventricular outflow tract (LVOT) gradient, while safety and tolerability were similar to placebo.3

EXPLORER-LTE was a single-arm, open-label, dose-blinded extension of the phase 3 EXPLORER-HCM study. Patients included in the extension were required to have a body weight >99.2 lb and documented left ventricular ejection fraction (LVEF) ≥50% by echocardiography, among other criteria. Patients with an echocardiogram abnormality, a history of syncope or sustained ventricular tachyarrhythmia, or clinically significant malignant disease developed since enrollment in the parent study, among other criteria, were excluded.4

Outcomes and Improvements

A total of 231 patients were enrolled in the long-term extension study – the cohort had a mean age of 60 years (standard deviation [SD], 11.9) and 41 patients (17.7%) had a history of atrial fibrillation. Mean baseline of LVEF was 74% (SD, 5.9), and mean LVOT gradient was 48.3 mmHg (SD, 31.9) at rest and 69.5 mmHg (SD, 33.3) during Valsalva.1

At 252 weeks, Owens and colleagues recorded mean changes from baseline at initiation of the long-term extension study of -38.7 mmHg for resting LVOT and -55.6 mmHg in Valsalva LVOT following treatment with mavacamten. 97.4% of patients achieved a Valsalva LVOT gradient ≤30 mmHg, which is the threshold for obstruction in oHCM.2

Another 69.6% of patients saw improvements of ≥1 NYHA class, and 59.2% were asymptomatic after 252 weeks. Mean LVEF decreased by 10.2% and remained within the normal range for the duration of the extension study. Safety findings were also consistent with results from the primary EXPLORER-HCM study.2

“This was a select group of patients, and it was our first large trial with mavacamten. We know from the phase 3 VALOR data, which enrolled sicker patients, that mavacamten has the same upfront, short-term benefit, and we have data out through 128 weeks that sustained benefit continues,” Owens said. “While we don’t have remodeling data on these sicker patients yet, I think we will get that from the real world.”

Editors’ Note: Owens reports disclosures with Bayer, Bristol Myers Squibb, Cytokinetics, Edgewise Therapeutics, Kardigan, Tenaya, and others.

References

1. Owens A. Safety and efficacy of treatment with mavacamten for up to 5 years in patients with obstructive hypertrophic cardiomyopathy: final results from MAVA-LTE. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

2. Bristol Myers Squibb. Bristol Myers Squibb Presents Data Up to Five Years Reinforcing the Long-Term Efficacy and Safety of Camzyos (mavacamten) in Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM) at the European Society of Cardiology (ESC) Congress 2026. August 29, 2026. Accessed September 17, 2026. https://news.bms.com/news/details/2026/Bristol-Myers-Squibb-Presents-Data-Up-to-Five-Years-Reinforcing-the-Long-Term-Efficacy-and-Safety-of-Camzyos-mavacamten-in-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-oHCM-at-the-European-Society-of-Cardiology-ESC-Congress-2026/default.aspx

3. Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (explorer-HCM): A randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2020;396(10253):759-769. doi:10.1016/s0140-6736(20)31792-x

4. Bristol Myers Squibb. A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed MAVERICK-HCM or EXPLORER-HCM. ClinicalTrials.gov Identifier: NCT03723655. Updated February 20, 2026. Accessed September 17, 2026. https://clinicaltrials.gov/study/NCT03723655