The EXPLORER-LTE cohort of the MAVA-LTE study (NCT03723655), the largest and longest evaluation of mavacamten, an experimental, first-in-class cardiac myosin inhibitor, in patients with symptomatic obstructive hypertrophic cardiomyopathy, released new interim data (obstructive HCM). These findings, which showed sustained improvements in cardiovascular outcomes at 48 and 84 weeks, were presented today at the American College of Cardiology’s 71st Annual Scientific Session as a late-breaking clinical trial.
At the end of the Phase 3 parent trial, EXPLORER-HCM, 231 of the 244 patients who were eligible for the long-term extension study were enrolled in EXPLORER-LTE (NCT03470545). Over 200 patients had stayed on the program for more than 48 weeks, and 67 had reached the 84-week mark. At 48 weeks and up to 84 weeks, clinically significant improvements in left ventricular outflow tract (LVOT) gradients, New York Heart Association (NYHA) Class, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were maintained. The safety profile of EXPLORER-HCM remained the same. Longer-term follow-up revealed no additional safety signals, and the exposure-adjusted incident rates in this group remained stable or decreased.
“These data underscore the potential of mavacamten to offer rapid and sustained improvement in key cardiac measures in patients living with this chronic, and sometimes progressive, disease,”said Florian Rader, M.D., M.Sc. co-director of the Clinic for Hypertrophic Cardiomyopathy, Cedars-Sinai Medical Center.
The EXPLORER-LTE cohort is part of the MAVA-LTE study, which is a 5-year dose-blinded investigation of mavacamten in patients with symptomatic obstructive HCM who completed the EXPLORER-HCM trial. A total of 251 adult patients with NYHA Class II or III obstructive HCM participated in the EXPLORER-HCM study. At baseline, all subjects had an LVEF of less than 55 percent and an LVOT gradient of less than 50 mmHg (resting and/or triggered). For 30 weeks, patients were randomly assigned to receive either a starting dose of 5 mg mavacamten or a placebo once daily.
“Interim results from this EXPLORER-LTE cohort build upon the clinical evidence supporting the potential for longer-term use of mavacamten in patients with symptomatic obstructive HCM. We look forward to the opportunity to bring this medicine to patients and eagerly await the U.S. Food and Drug Administration’s decision on our New Drug Application later this month,”said Marie-Laure Papi, vice president, and mavacamten development program lead, Bristol Myers Squibb.
The EXPLORER-LTE cohort started on 5 mg of mavacamten per day, with dose changes done at Weeks 4, 8, and 12 based solely on site-read echocardiogram measurements of Valsalva LVOT gradient and LVEF. Following a site-read echocardiography assessment of the post-exercise LVOT gradient at Week 24, dose adjustments were also available. LVEF 50%, mavacamten plasma trough concentration 1000 ng/mL, or an increase in corrected QT interval by Fredericia (QTcF) >15 percent were used as temporary termination criteria. The current efficacy and safety data are interim data from the ongoing MAVA-LTE research from April 2019 to August 2021. 94 percent of patients were still on mavacamten as of the August 2021 interim analysis cutoff date.