News from the 2020 Virtual ESC Congress: EXPLORER-HCM
News began emerging Saturday morning reporting on noteworthy clinical trial information from the European Society of Cardiology (ESC) Congress, the world’s largest conference dedicated to cardiovascular disease. The ESC is being presented digitally during the time of the coronavirus pandemic.
On Saturday morning, Lacopo Olivotto, MD, of Careggi University Hospital, Florence, Italy presented the results of the EXPLORER-HCM trial, which examined mavacamten as an alternative to surgical or catheter-based interventions to treat obstructive hypertrophic cardiomyopathy (HCM).
Mavacamten is a first-in-class investigational allosteric modulator of cardiac myosin which showed promise in the recent phase 2 MAVERICK HCM trial.
In EXPLORER-HCM, 251 patients received once daily mavacamten or placebo for 30 weeks. Primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and > 1 NYHA class reduction or a >3·0 mL/kg per min pVO2increase without NYHA class worsening at week 30. Secondary endpoints included changes in exercise capacity, symptoms, left ventricular outflow tract obstruction, functional status and quality of life.
Forty-five (36.6%) patients randomized to mavacamten met the primary composite endpoint at week 30 compared with 22 (17.2%) patients on placebo (p=0.0005). Each of the secondary endpoints, including post-exercise LVOT gradient and patient-reported outcomes, also demonstrated improvements for mavacamten versus placebo (all p<0.0006) with no significant differences in either safety or tolerability. Results were published concurrently in The Lancet.
Of particular note by Dr. Olivotto was the number of patients (27.4%) in the mavacamten arm who actually achieved a “complete response,” defined by the study as a complete deletion of all gradients.