Mavacamten (1) – Camzyos®

• Clinical trials
  • The EXPLORER-HCM trial was a double-blind, randomised controlled trial that included a total of 251 adults with symptomatic HCM in NYHA classes II or III and a left ventricular ejection fraction (LVEF) of ≥ 55%.
  • Participants were randomised in a 1:1 ratio to the two study arms: mavacamten (N = 123) versus placebo (N = 128).

Adults with symptomatic hypertrophic obstructive cardiomyopathy (NYHA Class II–III)

• For the treatment of adults with symptomatic hypertrophic obstructive cardiomyopathy (NYHA Class II–III), there is a hint of considerable additional benefit for mavacamten compared with the appropriate comparator therapy.
• Overall, there is a hint of considerable additional benefit from mavacamten compared with the appropriate comparator therapy.
• mortality
  • For the endpoint of all-cause mortality, the pharmaceutical manufacturer has not provided any data for the relevant patient population treated in accordance with the appropriate comparator therapy.
  • In the overall population, there was 1 death in the comparator arm.
• Morbidity – Perceived exertion – using the Borg RPE scale
  • Although a statistically significant advantage of mavacamten over the appropriate comparator therapy is evident for the endpoint of perceived exertion,
  • However, the 95% confidence interval for the standardised mean difference does not lie entirely outside the irrelevance range of −0.2 to 0.2.
  • It cannot therefore be concluded that the observed effect is clinically relevant.
• Morbidity – Symptoms – as measured by the total score on the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ)
  • The results of the HCMSQ, which assesses HOCM symptoms, show a statistically significant advantage of mavacamten compared with placebo, in each case in addition to treatment as prescribed by a doctor.
  • The effect is considered relevant, as the 95% confidence interval of the standardised mean difference lies entirely outside the irrelevance range of −0.2 to 0.2.
• Morbidity – symptoms – as assessed by the Patient Global Impression of Change (PGIC) and Patient Global Impression of Severity (PGIS)
  • The analyses of the PGIC and PGIS at week 30 compared with baseline each show statistically significant advantages for mavacamten in addition to treatment as prescribed by the doctor, compared with placebo in addition to treatment as prescribed by the doctor.
• Morbidity – health status – assessed using the visual analogue scale of the EQ-5D questionnaire (EQ-5D VAS)
  • For the health status endpoint, a statistically significant advantage of mavacamten over placebo was observed in each case, in addition to treatment as directed by the doctor.
  • The 95% confidence interval for the standardised mean difference does not lie entirely outside the non-significant range of −0.2 to 0.2.
  • It cannot therefore be concluded that the observed effect is clinically relevant.
• Health-related quality of life – Kansas City Cardiomyopathy Questionnaire – Overall Summary Score (KCCQ-OSS)
  • For the KCCQ-OSS, a statistically significant advantage of mavacamten over placebo was observed in each case, in addition to treatment as prescribed by a doctor.
  • As the 95% confidence interval for the standardised mean difference lies outside the non-significant range of −0.2 to 0.2, the effect is classified as significant.
• Side effects – severe adverse events (SUEs)
  • In the EXPLORER-HCM study, there was no statistically significant difference between the treatment groups in the evaluation of the SUE endpoint for the assessed population.
• Side effects – Discontinuation due to adverse events (AEs)
  • The results for the endpoint ‘discontinuation due to AEs’ show no statistically significant difference between mavacamten and placebo, in each case in addition to treatment as prescribed by the doctor.
• Side effects – Specific adverse events (systolic dysfunction)
  • No separate data are available for the endpoint ‘systolic dysfunction’ (PT, SUEs) for the patient population treated according to appropriate comparator therapy.
  • In the overall population, 1 event was observed in the group of patients treated with mavacamten.
• Overall assessment
  • No separate data are available for the patient population treated with appropriate comparator therapy in the category of mortality.
  • For the endpoints of perceived exertion (assessed using the Borg RPE scale) and health status (assessed using the EQ-5D VAS), no relevant advantages were observed for mavacamten.
  • In the category of health-related quality of life (assessed using the KCCQ-OSS), mavacamten also showed a statistically significant advantage over the appropriate comparator therapy.
  • In the category of side effects, there were no statistically significant differences between the two treatment arms, neither in terms of serious adverse events nor in terms of discontinuations due to adverse events.
  • Overall, at week 30, there are statistically significant advantages for mavacamten compared with the appropriate comparator therapy in both the morbidity endpoint category and health-related quality of life, which are classified as considerable.
  • These advantages are not offset by any disadvantages in other endpoint categories.

Courtesy translation only, please refer to the German original.