Projecting the Long-term Clinical Value of Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy in the United States: An Assessment of Net Health Benefit

Abstract

Purpose:The aim of the study was to project the long-term net health benefits of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States.Methods: A Markov model with 4 mutually exclusive health states (New York Heart Association [NYHA] functional classes I, II, and III/IV and death) was developed to project the life-years (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for patients with symptomatic obstructive HCM receiving mavacamten with or without βblocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or without BB or CCB monotherapy. The model simulated a patient cohort with a starting age of 59 years and 41% women. Transition probabilities across NYHA functional classes were estimated using data from the Phase III Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated after week 30. The mortality risks of NYHA functional class I were assumed to be the age-and sex-specific mortality risks of the US general population. The mortality risks for NYHA class II and III/IV were estimated using those

Mavacamten, a First-in-Class Cardiac Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy

“…We found relevant citations describing 2 distinct phase II trials (PIONEER-HCM and MAVERICK-HCM), 2 phase III trials (EXPLORER-HCM and VALOR-HCM), substudies of EXPLORER-HCM, and 2 modeling studies. [4][5][6][7][8][9][10][11] The results of the VALOR-HCM are currently only available in abstract form with a late breaking clinical trial report on April 2, 2022 at the American College of Cardiology meeting. 9 We also reviewed review articles on HCM and mavacamten that were identified through this search process and those identified through backwards citation tracking of other citations.…”

“…A Markov model with 4 mutually exclusive health states (NYHA functional class I, II, III/IV, or death) was conducted by Desai and colleagues 11 using the 30-week effects seen in EXPLORER-HCM to extrapolate the impact on final health outcomes over a lifetime. As such, patients could receive overlapping therapy with β-blockers or non-dihydropyridine calcium channel blockers along with mavacamten or placebo.…”

“…In addition, the relative lifetime costs for mavacamten versus disopyramide or septal reduction therapies were not calculated. 11…”

“…Figure 2 adapts the American Heart Association/American College of Cardiology treatment recommendations for patients with symptomatic HCM and outflow obstruction to include the potential role of mavacamten. 1,[3][4][5][6][7][8][9][10][11]26 βblockers and non-dihydropyridine calcium channel blockers are relatively safe and well-tolerated therapies and were employed in most patients before they were started on additional disopyramide or septal reduction therapies. 1,[4][5][6]9 Similarly, mavacamten was mostly studied in patients who were on baseline therapy or were intolerant to β-blockers or non-dihydropyridine calcium channel blockers.…”

“…[4][5][6]27 Modeling studies seem to disagree on the extent of long-term benefit that mavacamten will provide which is critical to know because of its high drug acquisition cost. 10,11 Both disopyramide and mavacamten need intensive clinician oversight upon initiation, careful dosage titration, and commitment to follow-up to maximize the benefits and minimize their adverse events (including precipitating systolic dysfunction). 3,28 Both options are CYP substrates and in the presence of strong inhibitors can result in significant adverse events.…”