VALOR-HCM: Mavacamten Significantly Reduces Need For Surgical Intervention in Patients With Obstructive HCM

 Use of mavacamten to treat patients with obstructive hypertrophic cardiomyopathy (HCM) who were referred as candidates for invasive septal reduction therapy (SRT), significantly reduced the need for the surgical intervention at 16 weeks, according to results from the VALOR-HCM trial presented April 2 during ACC.22.

The randomized, double-blind, placebo-controlled study evaluated the use of mavacamten in a total of 112 adults with symptomatic obstructive HCM who were referred to an HCM expert at 19 HCM centers. All patients had documented HCM with maximum septal wall thickness ≥15 mm or ≥13 mm; family history of HCM; severe symptoms despite maximally tolerated medical therapy; dynamic left ventricular outflow tract (LVOT) gradient at rest or with provocation ≥50 mmHg; and documented left ventricular ejection fraction ≥60%.

Researchers randomly assigned each patient to receive mavacamten or a placebo for 16 weeks. The primary endpoint was a composite of patient decision to proceed with SRT or continue to meet 2011 ACC/AHA guideline eligibility for SRT after 16 weeks.

At 16 weeks, only 18% of patients on mavacamten were still eligible for SRT, compared with 77% of those on placebo. Researchers also observed significant improvements across all secondary endpoints, including reduction in resting LVOT gradient; ≥1 class improvement in NYHA Class; improvement in KCCQ-clinical summary score; reduction in N-terminal pro-B-type natriuretic peptide; and reduction in troponin I. No patients experienced serious adverse cardiac events.

"These were very symptomatic, sick patients who were on maximally tolerated medical therapy and were faced with the decision of whether or not to have septal reduction therapy to relieve the obstruction. In taking this drug, they got a whole lot better across the board," said Milind Y. Desai, MD, MBA, FACC, the study's lead author. "This is really the first pharmacotherapy that offers a viable medical option for people with obstructive HCM short of needing a procedure."

Desai and colleagues note that additional data is needed to assess the durability of improvement in SRT eligibility over longer time periods. "We are hoping this study will also draw much-needed attention to HCM," said Desai. "This disease is woefully underrecognized. There are not enough HCM experts and not enough proven medical therapies, so there are many opportunities to do better."

Mavacamten is currently under review with the U.S. Food and Drug Administration for use in obstructive HCM, with a decision expected at the end of April.

 

ACC 2022

Prepared by: Dr. Nabil Paktin,