CAMZYOS (mavacamten) - Obstructive hypertrophic cardiomyopathy

The Committee deems that the clinical benefit of CAMZYOS (mavacamten) 2.5 mg, 5 mg, 10 mg and 15 mg hard capsules is substantial only in the treatment of obstructive hypertrophic cardiomyopathy (oHCM) in adult patients with persistent symptoms (New York Heart Association, NYHA, class II-III) on background oHCM therapy.

Considering:

• demonstration of the superiority of mavacamten compared to placebo in two randomised, controlled phase 3 studies (EXPLORER-HCM and VALOR-HCM), in terms of improvement in exercise capacity (peak VO2) and NYHA clinical symptoms at week 30, respectively, and reduction in the use of septal reduction therapy at week 16, in adult patients with symptomatic oHCM (despite optimised background therapy for the majority of the subjects included);
• demonstration of the superiority of mavacamten compared to placebo for quality of life criteria assessed using validated disease-specific scores (clinical score on the KCCQ 23 questionnaire and shortness of breath domain score on the HCMSQ questionnaire);
• an acceptable safety profile of mavacamten comparable to placebo according to safety data from clinical studies;
• a partially met medical need;

and despite:

• the lack of evidence of the efficacy of mavacamten on morbidity and mortality endpoints (however, given the epidemiological profile of the disease and according to expert opinion, it appears to be difficult to assess the efficacy of mavacamten on the basis of mortality endpoints);
• a follow-up period in the clinical studies (30 weeks for EXPLORER-HCM and 16 weeks for VALOR-HCM) that does not enable any conclusion to be reached with respect to the long-term efficacy and safety of mavacamten;
• a potential detrimental effect of mavacamten on cardiac function (reduction in left ventricular ejection fraction) that cannot be excluded in at-risk subjects (patients with a serious intercurrent disease, such as an infection or arrhythmia, or who are undergoing major cardiac surgery);

the Committee deems that CAMZYOS (mavacamten) 2.5 mg, 5 mg, 10 mg and 15 mg hard capsules provides a moderate clinical added value (CAV III) in the current care pathway for obstructive hypertrophic cardiomyopathy (oHCM) in adult patients with persistent symptoms (New York Heart Association, NYHA, class II-III) on background oHCM therapy.