6/28/23, 10:09 PM EXPLORER-HCM Pathway Feedback Search Clinical Topics Home Studies EXPLORER HCM EXPLORER HCM Disease Hypertrophic cardiomyopathy Trial question What is the role of mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy? Study design Multi-center Double blinded RCT Population Characteristics of study participants 41.0% female N = 251 59.0% male 251 patients (102 female, 149 male) Inclusion criteria: patients with hypertrophic cardiomyopathy with LVOT gradient 50 mmHg and NYHA class II-III symptoms Key exclusion criteria: history of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months before screening; QT interval corrected using Fridericia's formula > 500 ms; paroxysmal or intermittent AF; and persistent or permanent AF not on anticoagulation for 4 weeks or not adequately rate-controlled within 6 months before screening Interventions N=123 mavacamten (a starting dose of 5 mg for 30 weeks) N=128 placebo (matching placebo for 30 weeks) Primary outcome Clinical response at week 30 https://web.pathway.md/studies/recmb5FEo6RVbjNnT 1/2 6/28/23, 10:09 PM EXPLORER-HCM Pathway 37.0 % 37 27.8 % 18.5 % 17 Significant increase 9.3 % NNT = 5 0.0 % Mavacamten Placebo Significant increase in clinical response at week 30 (37% vs. 17%; AD 19.4%, 95% CI 8.7 to 30.1) Secondary outcomes Significant increase in improvement in peak oxygen consumption at week 30 (1.4 mL/kg/min vs. -0.1 mL/kg/min; AD 1.4 mL/kg/min, 95% CI 0.6 to 2.1) Significant increase in 1 NYHA class improvement at week 30 (65% vs. 31%; AD 34%, 95% CI 22.2 to 45.4) Safety outcomes No significant difference in serious adverse events. Conclusion In patients with hypertrophic cardiomyopathy with LVOT gradient 50 mmHg and NYHA class II- III symptoms, mavacamten was superior to placebo with respect to clinical response at week 30. Reference Iacopo Olivotto, Artur Oreziak, Roberto Barriales-Villa et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Sep 12;396(10253):759-769. Open reference URL https://web.pathway.md/studies/recmb5FEo6RVbjNnT 2/2