Bristol Myers Squibb announced results from the Phase 3 VALOR-HCM study, which showed the addition of mavacamten, an investigational, first-in-class cardiac myosin inhibitor, significantly reduced the need for septal reduction therapy (SRT) in patients with severely symptomatic obstructive hypertrophic cardiomyopathy (obstructive HCM) who had been appropriate for SRT per the 2011 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines at baseline. Study participants were on maximally tolerated background regimens when they entered the trial and remained on them through the duration of the study. These data were presented today as a late-breaking clinical trial at the American College of Cardiology’s 71st Annual Scientific Session.
At 16 weeks the primary and all secondary endpoints were met. Of patients treated with mavacamten, 82% had not proceeded with SRT and no longer met the criteria for SRT according to the 2011 ACC/AHA Guidelines compared to 23% of patients receiving placebo. Patients in the mavacamten arm also demonstrated reduction in left ventricular outflow tract (LVOT) gradients, improvement in New York Heart Association (NYHA) Classification, improvement in quality-of-life measures and improvement in cardiac biomarkers at a high degree of statistical significance compared to the placebo arm. No new safety signals were observed.
“VALOR-HCM builds upon findings of the Phase 3 EXPLORER-HCM trial and shows mavacamten to be an effective potential treatment option for those with severe symptomatic obstructive HCM who meet guideline criteria for SRT,” said Milind Desai, M.D., MBA, director of HCM center and director of clinical operations, Heart, Vascular & Thoracic Institute, Cleveland Clinic. “The data presented today are clinically meaningful and have demonstrated the potential to impact parameters leading to SRT eligibility.”
“These results validate the promising potential of mavacamten as an important treatment option for symptomatic oHCM patients,” said Marie-Laure Papi, vice president and mavacamten development lead, Bristol Myers Squibb.
In the Phase 3 study, patients with symptomatic obstructive HCM (NYHA Class III-IV or Class II with exertional syncope or near syncope) who met the 2011 ACC/AHA Guideline criteria and were referred for SRT were randomized 1:1 to mavacamten (n=56) or placebo (n=56) for 16 weeks. Study participants remained consistent on their maximally tolerated baseline standard of care regimens, which included ß-blockers, calcium channel blockers and/or disopyramide administered as monotherapy or in combination. Echocardiograms were conducted to evaluate LVOT gradient and LVEF at baseline and during drug titration to guide dosing and assess safety at Weeks 4, 8 and 12. Change from baseline in SRT eligibility, post-exercise LVOT peak gradient, NYHA Class, KCCQ-23 CSS and biomarkers (NT-proBNP and cardiac troponin I) were analyzed at Week 16.