Long-Term Data from ESC 2024 Reinforces Safety, Efficacy Profile of Mavacamten in oHCM

Pablo García-Pavia, MD, PhD
Credit: X.com

New long-term data are highlighting the sustained benefits of mavacamten (Camzyos) among patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Presented during the European Society of Cardiology (ESC) Congress 2024 and simultaneously published in the European Heart Journal, the latest data release from the MAVA-LTE trial offers evidence of the effects on left ventricular outflow tract (LVOT) gradients, NT-proBNP, and quality of life through up to 180 weeks of follow-up.¹

“The consistent and sustained improvements in multiple cardiac measures over more than three years with [mavacamten] shows that this therapy meets an important treatment need for patients with symptomatic obstructive HCM,” said Pablo García-Pavia, MD, PhD, head of the Inherited Cardiac Diseases and Heart Failure Unit at the Department of Cardiology of Hospital Universitario Puerta de Hierro.² “These positive long-term data, together with the inclusion of [mavacamten] in ESC clinical guidelines for obstructive HCM, underscore the important role of this medicine in the long-term care of this lifelong condition that requires ongoing management.”

A first-in-class cardiac myosin inhibitor, mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for treatment of adults with symptomatic NYHA class 2-3 obstructive HCM based on the results of EXPLORER-HCM trial, which demonstrated use of mavacamten was associated with improved exercise capacity, LVOT obstruction, NYHA functional class, and health status among patients with symptomatic obstructive HCM. In June 2023, the FDA approved a label expansion for mavacamten to include data from the VALOR-HCM study in the prescribing information, which will now reflect the effects of the agent on need and eligibility for septal reduction therapy (SRT) in patients with obstructive HCM.^1,3,4

The MAVA-LTE trial was designed as a 5-year, open-label, extension study and enrolled patients from the EXPLORER-HCM trial. From the original EXPLORER-HCM trial, which included 251 patients, 231 were enrolled in MAVA-LTE. Of these, 211 still received mavacamten at the time of the latest data cutoff. Among this cohort, the median time on study was 166 (Interquartile Range [IQR], 6.0 to 228.1) weeks, with 185 and 99 patients completing their weeks 156 and 180 visits, respectively.¹

Results of the latest analysis revealed sustained reductions in LVOT gradient (Mean: resting, −40.3 [Standard Deviation [SD], 32.7] mmHg; Valsalva, −55.3 [SD, 33.7] mmHg), NT-proBNP (median,−562 [IQR, −1162.5 to −209] ng/L), and EQ-5D-5L score (mean, 0.09 [SD, 0.17]). Further analysis indicated the mean left ventricular ejection fraction (LVEF) among the study cohort decreased from 73.9% at baseline to 66.6% at week 24 and to 63.9% at week 180.¹

When assessing safety outcomes, investigators found 20 patients (8.7%; exposure-adjusted incidence: 2.77 per 100 patient-years) experienced 22 transient reductions in LVEF to less than 50%, which resulted in temporary treatment interruption. Investigators noted all of these patients recovered an LVEF of 50% or greater. Additionally, investigators pointed out there were 5 patient deaths in the study, but none were considered related to mavacamten.¹

“These results, representing the longest duration of follow up of the Phase 3 EXPLORER study to date, further reinforce the established safety and efficacy profile of CAMZYOS,” said Roland Chen, MD, senior vice president and head of Immunology, Cardiovascular & Neuroscience (ICN) Development at Bristol Myers Squibb.² “As the first and only approved cardiac myosin inhibitor for patients with symptomatic obstructive HCM and with thousands of patients around the world treated to date, CAMZYOS, which targets the source of symptomatic obstructive HCM, is redefining the treatment landscape for this patient population.”

References:

1. Garcia-Pavia P, Oręziak A, Masri A. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. European Heart Journal. Published online September 1, 2024. doi:10.1093/eurheartj/ehae579
2. Bristol Myers Squibb. Long-Term Follow-Up Data from Phase 3 Study of CAMZYOS® (mavacamten) Underscores Established Efficacy and Safety Profile in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM). Bristol Myers Squibb. September 1, 2024. Accessed September 1, 2024. https://news.bms.com/news/corporate-financial/2024/Long-Term-Follow-Up-Data-from-Phase-3-Study-of-CAMZYOS-mavacamten-Underscores-Established-Efficacy-and-Safety-Profile-in-Patients-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-oHCM/default.aspx.
3. Campbell P. FDA approves updated label for Mavacamten in obstructive hypertrophic cardiomyopathy. HCP Live. June 15, 2023. Accessed September 1, 2024. https://www.hcplive.com/view/fda-approves-updated-label-for-mavacamten-in-obstructive-hypertrophic-cardiomyopathy.
4. Campbell P. FDA approves Mavacamten (Camzyos) for obstructive hypertrophic cardiomyopathy. HCP Live. April 22, 2022. Accessed September 1, 2024. https://www.hcplive.com/view/fda-approves-mavacamten-for-obstructive-hypertrophic-cardiomyopathy.