New findings presented at the ESC Congress show that mavacemten improves heart function and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM).
To date, the medical treatments for obstructive HCM focus on symptom relief but do not address the underlying causes. These treatments also offer modest efficacy with significant adverse effects. Invasive procedures like surgical surgical septal myectomy and alcohol septal ablation are efficacious but carry certain risks and also require specific expertise. Hence, an effective pharmacological therapy for obstructive HCM remains an unmet need for patients with HCM.
Mavacamten is a first-in-class cardiac myosin inhibitor that directly targets the underlying pathophysiology of HCM. Clinical studies already show that mavacamten leads to significant improvements of symptoms, physical function, exercise capacity, and quality of life, and reduced left ventricular outflow tract (LVOT) obstruction in patients with obstructive HCM.
In the EXPLORER-HCM global phase 3 clinical trial, 251 patients with symptomatic obstructive HCM were randomised to once-daily mavacamten (5 mg initially with a twostep dose titration) or placebo for 30 weeks. The primary endpoint was the treatment effect of mavacamten at week 30 on symptoms and cardiac function. The secondary endpoints of the study included change from baseline to week 30 in post-exercise LVOT gradient and patient-reported outcomes.
Findings show that at week 30, 36.6% patients on mavacamten met the primary endpoint vs.17.2% patients in the placebo group. There was also notable improvement in secondary endpoints, including post-exercise LVOT gradient and patient-reported outcomes improvements, for mavacamten compared to patients in the placebo group.
Serious adverse events were reported in 8.1% of patients on mavacamten and in 8.6% of patients on placebo, hence safety and tolerability with mavacamten were similar to placebo. Serious cardiac adverse events were also the same in both groups and occurred in 4 patients treated with mavacamten and 4 patients treated with placebo.
“The results of this pivotal trial support a role for disease-specific therapy for HCM, which treats the cause instead of just managing symptoms,” said Principal Investigator, Professor Iacopo Olivotto (Careggi University Hospital, Florence, Italy). He noted, “The totality and consistency of the results showed benefit of mavacamten treatment compared with placebo in patients on background HCM therapy. Mavacamten improved functional capacity, LVOT gradient, symptoms, and key aspects of quality of life in patients with obstructive HCM and was generally well tolerated.”
Source: ESC Congress 2020
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