Bristol Myers Squibb’s Camzyos Falls Short in Phase II Trial for Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

Image Credit: Adobe Stock Images/sorrakrit

Bristol Myers Squibb (BMS) announced that its cardiac myosin inhibitor Camzyos (mavacamten) did not meet its dual primary endpoints in the Phase III ODYSSEY-HCM trial in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). The trial results found that patients administered Camzyos did not achieve significant improvements in either Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-23 CSS) or peak oxygen consumption (pVO₂), compared with placebo.¹

“The ODYSSEY-HCM trial, the largest and longest-duration study completed to date in patients with non-obstructive HCM, tested the hypothesis of whether a cardiac myosin inhibitor would improve measures of feel and function for these patients, showing clinical benefits similar to what we have seen in obstructive HCM,” said Milind Desai, MD, MBA, vice chair, Heart, Vascular & Thoracic Institute, director, HCM Center, Cleveland Clinic, in a press release. “The findings of this trial help us understand that obstructive HCM and non-obstructive HCM are two unique diseases. Through long-term trials and real-world data from thousands of patients with symptomatic obstructive HCM, we have seen the meaningful impact that Camzyos has on improving the quality of life for patients living with this condition. ODYSSEY-HCM indicates that we must consider new ways of thinking about potential treatment approaches for non-obstructive HCM. We want to thank the patients and investigators for their efforts in completing this important trial and their commitment to advancing the scientific understanding of this complex disease.”

The randomized, double-blind, placebo-controlled ODYSSEY-HCM trial compared changes from baseline in KCCQ-23 CSS and pVO2 among 580 adult patients with symptomatic (NYHA class II or III) nHCM administered either Camzyos or placebo. Key secondary endpoints of the study included change from baseline in ventilatory efficiency, NYHA functional class, N-terminal pro B-type natriuretic peptide, levels, and Hypertrophic Cardiomyopathy Symptom Questionnaire-Shortness of Breath at week 48.

While full results of the study were not released, BMS stated that it will work with key investigators to share them with the scientific community. The safety profile of Camzyos was consistent with prior findings and no new signals were reported.¹

Camzyos was first approved by the FDA in April 2022 for patients with NYHA class II–III obstructive HCM, marking the first allosteric and reversible cardiac myosin inhibitor designed to directly address the underlying hypercontractility of the condition.2 In 2023, the FDA approved a supplemental New Drug Application to include data from the Phase III VALOR-HCM trial in the US prescribing information. The trial demonstrated that Camzyos significantly reduced the need for septal reduction therapy in eligible patients.³

It is estimated that HCM can affect approximately up to one in every 500 people. In the United States, around 700,000 people are currently living with HCM; however, 85% could potentially be undiagnosed. According to BMS, it is the most common hereditary heart disease to run in families.⁴

“While these results are disappointing, the ODYSSEY-HCM trial meaningfully contributes to the understanding of non-obstructive HCM, a disease where there remains a significant need for new treatment options,” said Roland Chen, MD, SVP, drug development, immunology and cardiovascular medicines, BMS, in the press release. “These findings represent the first Phase 3 clinical trial data for a cardiac myosin inhibitor in non-obstructive HCM. Importantly, these results do not change the favorable benefit-risk profile that has been consistently demonstrated across our Camzyos clinical trials in obstructive HCM and the robust body of real-world effectiveness and safety evidence showing its benefit for people living with obstructive HCM around the world.”

References

1. Bristol Myers Squibb Provides Update on Phase 3 ODYSSEY-HCM Trial. BMS. April 14, 2025. Accessed April 15, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-ODYSSEY-HCM-Trial/default.aspx

2. U.S. Food and Drug Administration Approves Camzyos™ (mavacamten) for the Treatment of Adults With Symptomatic New York Heart Association Class II-III Obstructive Hypertrophic Cardiomyopathy (HCM) to Improve Functional Capacity and Symptoms. BMS. April 28, 2022. Accessed April 15, 2025. https://news.bms.com/news/corporate-financial/2022/U.S.-Food-and-Drug-Administration-Approves-Camzyos-mavacamten-for-the-Treatment-of-Adults-With-Symptomatic-New-York-Heart-Association-Class-II-III-ObstructiveHypertrophic-Cardiomyopathy-HCM-to-Improve-Functional-Capacity-and-Symptoms/default.aspx

3. U.S. Food and Drug Administration Approves Addition of Positive Data from Phase 3 VALOR-HCM Study to CAMZYOS® (mavacamten) Label. BMS. June 15, 2023. Accessed April 15, 2025. https://news.bms.com/news/corporate-financial/2023/U.S.-Food-and-Drug-Administration-Approves-Addition-of-Positive-Data-from-Phase-3-VALOR-HCM-Study-to-CAMZYOS-mavacamten-Label/default.aspx

4. Why is hypertrophic cardiomyopathy, the most commonly inherited heart disease, often undiagnosed? BMS. May 1, 2022. Accessed April 15, 2025. https://www.bms.com/life-and-science/science/reasons-behind-hypertrophic-cardiomyopathy-going-undiagnosed.html#:~:text=Fast%20facts%20on%20HCM%20*%20HCM%20affects,~85%%20of%20those%20adults%20may%20remain%20undiagnosed.%5E