Long-term Efficacy and Safety of Mavacamten in the Treatment of Obstructive HCM
Interim results of the MAVA-LTE study provide the latest data on the long-term safety and efficacy of symptomatic treatment with mavacamten for obstructive hypertrophic cardiomyopathy (oHCM), with the longest follow-up period nearly 2.5 years. For clinical practice, the long-term reduction of left ventricular outflow tract (LVOT) obstruction and good tolerability of the treatment are particularly favorable.
Mavacamten in Clinical Practice
Orally administered mavacamten targets cardiac myosin and reversibly allosterically inhibits myosin-ATPase. The drug modulates the number of myosin heads capable of contraction, thereby reducing the likelihood of forming excessive cross-bridges, which are the cause of hypercontractility and relaxation disorders of the myocardium in HCM. Under physiological conditions, 40–50% of myosin heads are in an inactive form, whereas in HCM it is only 15–20%.
Mavacamten has been registered for use in the EU for more than half a year, and insights into the long-term effectiveness of symptomatic treatment of obstructive HCM with this drug are gradually emerging. It was registered based on the results of 2 main studies, and the aim of the authors of the following review was to evaluate the interim results of the cohort with extended follow-up of patients who completed the EXPLORER-HCM study.
Follow-up Study MAVA-LTE
Adults with symptomatic obstructive hypertrophic cardiomyopathy could enroll in the multicenter MAVA-LTE (Long-Term Safety Extension) study at the end of their participation in the EXPLORER-HCM study after discontinuing mavacamten or placebo. A total of 231 (94.7%) of 244 eligible patients enrolled between April 2019 and March 2021. The participants were, on average, 60 years old, and 39% were women.
Patients took mavacamten at a dose of 5 mg once daily, with treatment adjusted based on echocardiographic evaluation. Data collection for the subsequent analysis ended at the end of August 2021, with 217 (93.9%) patients remaining on therapy. The median follow-up period was 62.3 weeks (range 0.3–123.9).
Findings
After 48 weeks, patients showed improvements in left ventricular outflow tract gradients (mean change from baseline ± standard deviation) at rest (−35.6 ± 32.6 mmHg) and during the Valsalva maneuver (−45.3 ± 35.9 mmHg). There was also a reduction in levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with a median of −480 ng/L (interquartile range: −1104 to −179 ng/L). 67.5% of participants improved by ≥ 1 NYHA class (New York Heart Association functional classification). For patients who continued treatment for 84 weeks, further sustained reductions in LVOT gradient and NT-proBNP were observed.
Regarding adverse events, eight participants reported heart failure, and 21 reported atrial fibrillation (AF), including 11 patients with no prior history of AF. Treatment was temporarily interrupted for 12 participants due to a decrease in left ventricular ejection fraction (LVEF) to < 50%, with all cases being reversible. Ten patients discontinued therapy due to treatment-related adverse events.
Conclusion
Long-term monitoring of mavacamten treatment demonstrated clinically significant and sustained reductions in LVOT obstruction, NT-proBNP levels, and improvements in NYHA functional classification, consistent with the results of the EXPLORER-HCM study. In most patients, LVOT obstruction decreased below the values defining obstructive HCM. The treatment was well-tolerated throughout the follow-up period (with a median duration of 62 weeks), with many participants still being monitored. The study will be completed in 2026.
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Sources:
1. Rader F., Oreziak A., Choudhury L. et al. Mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy. JACC Heart Fail 2024; 12 (1): 164–177, doi: 10.1016/j.jchf.2023.09.028.
2. Dong T., Alencherry B., Ospina S., Desay M. Y. Review of mavacamten for obstructive hypertrophic cardiomyopathy and future directions. Drug Des Devel Ther 2023; 17: 1097–1106, doi: 10.2147/DDDT.S368590.
3. EPAR Camzyos. European Medicines Agency, 2023 Jul 24. Available at: www.ema.europa.eu/en/medicines/human/EPAR/camzyos#:~:text=Camzyos%20received%20a%20mar keting%20authorisation,EU%20on%2026%20June%202023
4. SPC Camzyos. Available at: www.ema.europa.eu/cs/documents/product-information/camzyos-epar-product-information_cs.pdf
A summary of the product information can be found here.
3500-CZ-2400012
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