Safety of mavacamten in a compassionate use program for adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

Daniel Messroghli (Berlin)1, R. Pfister (Köln)2, F. Knebel (Berlin)3, S. Desch (Leipzig)4, H. Baccouche (Sindelfingen)5, J. Schmölders (Munich)6, F. Seeger (Ravensburg)7, T. Lewalter (München)8, J. Brätz (Hamburg)9, G. Gitsioudis (Stuttgart)10, C. Öztürk (Bonn)11, K. Lenk (Leipzig)12

1Deutsches Herzzentrum der Charite (DHZC) Klinik für Kardiologie, Angiologie und Intensivmedizin | CBF Berlin, Deutschland; 2Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; 3Sana Klinikum Lichtenberg Klinik für Innere Medizin II, Schwerpunkt Kardiologie Berlin, Deutschland; 4Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; 5Klinikverbund Süd-West Sindelfingen, Deutschland; 6Bristol Myers Squibb Munich, Deutschland; 7Oberschwaben Klinik gGmbH - Krankenhaus St. Elisabeth Kardiologie Ravensburg, Deutschland; 8Internistisches Klinikum München Süd Klinik für Kardiologie München, Deutschland; 9Albertinen Krankenhaus, Herz- und Gefäßzentrum Klinik für Kardiologie Hamburg, Deutschland; 10Karl-Olga-Krankenhaus Medizinische Klinik II, Kardiologie, Angiologie u. Intern. Intensivmedizin Stuttgart, Deutschland; 11Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; 12Universitätsklinikum Leipzig Klinik und Poliklinik für Kardiologie Leipzig, Deutschland


Introduction: Hypertrophic cardiomyopathy (HCM) is a chronic myocardial disease resulting from excess myosin-actin cross-bridging. Mavacamten is the first FDA- and EMA-approved targeted pharmacologic treatment for obstructive HCM (oHCM) and was approved in Germany in June 2023. Mavacamten is a selective, allosteric, and reversible cardiac myosin inhibitor. It modulates the number of myosin heads that can enter power-generating states, thus reducing (or in HCM normalizing) the probability of force-producing systolic and residual diastolic cross-bridge formation. In patients with oHCM, cardiac myosin inhibition with mavacamten normalizes contractility, reduces dynamic left ventricular outflow tract obstruction, and improves cardiac filling pressures. The aim of the mavacamten compassionate use program (CUP) was to grant access to mavacamten to patients with symptomatic oHCM in Germany prior to EU approval. Here, we present the baseline characteristics and safety data reported between August 24, 2022 and July 24, 2023.

Methods: The CUP provided mavacamten prior to marketing authorization to adults with symptomatic oHCM eligible for septum reduction therapy (SRT), who could not join an ongoing clinical trial for this indication in Germany or be treated satisfactorily with other drugs prescribed for oHCM. Patients received mavacamten once daily (QD), starting with 2.5 mg or 5 mg according to the treatment plan. Mavacamten doses were increased depending on the clinical response to a maximum of 5 mg or 15 mg, respectively. Baseline characteristics and safety data were provided by participating sites during the time frame noted above.

Results: In total, 41 patients (mean age, 60.4 years; 51% male; mean weight, 81.2 kg; mean height, 170.1 cm; prior SRT, 12 (29%) patients; all NYHA functional class II-III) received mavacamten as part of the CUP. Mean follow-up time was 3.9 months. The patients took concomitant medications of beta blockers (24 patients) and calcium channel blockers (14 patients). Overall, 12 adverse events (AEs) were reported in seven patients. One serious AE (SAE) of pericardial effusion and nine non-serious AEs (including headache, fatigue, nausea, dizziness) were considered treatment related. Four patients permanently discontinued treatment with mavacamten due to side effects; there were no reported temporary treatment interruptions. Further evaluation of the reported adverse events and follow-up is ongoing.

Conclusions: The early mavacamten safety results presented here provide real-world safety data in people with symptomatic oHCM. Further observational studies in larger multinational populations are needed to better understand the long-term real-world safety of mavacamten.

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