On August 28, 2023, the findings of a clinical trial on the efficacy and safety of Mavacamten in treating symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in adults in China were published online in the prestigious international cardiovascular journal, “JAMA Cardiology” (a Tier 1 journal, or among the top 5%, as ranked by the Chinese Academy of Sciences, IF: 24). This study was led by Prof. Zhang Shuyang, President of PUMCH, and carried out in 17 Chinese hospitals. The study demonstrated that Mavacamten showed good efficacy and safety in treating Chinese oHCM patients . Prof. Tian Zhuang presented these research findings in a keynote speech at the 2023 European Society of Cardiology Congress (ESC Congress 2023). This study is the first Phase III clinical trial conducted in China on the treatment of oHCM with Mavacamten, providing rigorous and scientific evidence for an effective treatment approach for Chinese oHCM patients .
Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by thickening of the heart muscle and is one of the main causes of sudden cardiac death in young people triggered by sports. It is classified into oHCM when the LVOT (left ventricular outflow tract) gradient is ≥30 mm Hg, and non-obstructive HCM when the LVOT gradient is < 30 mm Hg. oHCM patients often exhibit more severe clinical symptoms. In China, there are at least one million HCM patients, with 70% of them being oHCM cases. Currently, the treatment options for oHCM include medication and surgery. However, traditional medications lack specificity and can only alleviate symptoms without being able to alter progression of the disease. Surgery requires high levels of expertise, and invasive procedures may pose risks.
Mavacamten is a first-in-class cardiac myosin inhibitor. Previous global Phase III clinical trials have confirmed its safety and efficacy in treating symptomatic oHCM patients. However, evidence in the Chinese population is lacking. Led by Prof. Zhang Shuyang, the PUMCH President, 17 Chinese hospitals initiated a Phase III trial aiming to investigate the efficacy and safety of Mavacamten in Chinese adults with symptomatic obstructive hypertrophic cardiomyopathy (“EXPLORER-CN”). The goal is to provide scientific evidence for the early adoption of treatment strategies equivalent to those in other countries for the nearly one million oHCM patients in China.
▲Prof. Tian Zhuang from PUMCH presented the EXPLORER-CN study at ESC Congress 2023
The EXPLORER-CN study enrolled a total of 81 oHCM patients, with 54 in the Mavacamten treatment group and 27 in the placebo group. At week 30, the change in Valsalva LVOT peak gradient from baseline in the Mavacamten treatment group was significantly different from the placebo group, with a difference of -70.29 mmHg. The benefit of Mavacamten treatment was observed as early as week 4 and sustained throughout the study period. Mavacamten treatment also improved various secondary endpoints, including resting LVOT gradient at week 30, NYHA (New York Heart Association) functional class, quality of life, cardiac biomarkers, and left ventricular mass index.
In terms of safety, Mavacamten was well tolerated and showed a safety profile that is consistent with the findings of previous studies, with no new safety signals observed in the Chinese oHCM patients. In addition, both the Mavacamten treatment group and the placebo group maintained stable left ventricular ejection fraction (LVEF) throughout the study period, with no patients having an LVEF <50%.
The study results show that Mavacamten demonstrated significant improvement in the primary efficacy endpoint when treating Chinese oHCM patients, and improvements with Mavacamten were also noted across all secondary efficacy endpoints. The study also confirms the safety profile of Mavacamten as being consistent with previous research.
A commentary by Prof. Milind Y. Desai, the Director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic and the principal investigator of the Phase III clinical trial VALOR-HCM (Mavacamten for treatment of symptomatic oHCM), was published in the same issue of “JAMA Cardiology”. The commentary stated that this PUMCH-led study confirmed that the efficacy and safety of Mavacamten extend to Asian patients. What’s worth noting is that this study used a lower starting dose of the drug, which was safe and did not compromise efficacy. This approach should be recognized and adopted more widely.
Translated by Liu Haiyan
Reviewed by Wu Wei and Wang Yao