Sanofi's second-generation cardiac myosin inhibitor Aficamten approved in China

On December 17, Sanofi announced that Aficamten has received approval from the National Medical Products Administration (NMPA) for marketing. It is indicated for adult patients with obstructive hypertrophic cardiomyopathy (HCM) classified as New York Heart Association (NYHA) class II–III to improve exercise capacity and symptoms.

Aficamten tablets are a potential "best-in-class" therapeutic for hypertrophic cardiomyopathy. This approval marks Aficamten as an innovative drug achieving its "global first launch" in China, with authorization occurring earlier than in other countries and regions worldwide, including the United States and the European Union.

Aficamten is a small-molecule cardiac myosin inhibitor (CMI) independently developed by Cytokinetics. Through comprehensive chemical optimization, the drug improves its therapeutic index and pharmacokinetic profile by reducing the number of force-producing cross-bridges of active myosin per cardiac cycle, thereby inhibiting the myocardial hypercontractility associated with HCM. In 2020, Cytokinetics granted Corxel Pharmaceuticals an exclusive license to develop and commercialize Aficamten in Greater China. In 2024, Sanofi acquired the exclusive development and commercialization rights for Aficamten in Greater China from Corxel Pharmaceuticals.

This approval of Aficamten tablets is primarily based on positive results from the pivotal global Phase 3 clinical trial SEQUOIA-HCM. The study met its primary endpoint of change in peak oxygen uptake (pVO₂) measured by cardiopulmonary exercise testing (CPET), along with ten secondary endpoints including changes in left ventricular outflow tract gradient (LVOT-G) and improvement in NYHA functional class. After 24 weeks of treatment with Aficamten tablets, pVO₂ increased by 1.7 mL/kg/min from baseline compared to the placebo group. Additionally, compared to placebo, subjects receiving Aficamten achieved an average reduction in LVOT-G of 48 mmHg at 12 weeks and 50 mmHg at 24 weeks, with a rapid reduction of 20 mmHg observed as early as 2 weeks. The proportion of patients showing an improvement of ≥1 NYHA class reached 48.6% at 12 weeks and 58.5% at 24 weeks. Furthermore, among patients who met the criteria for septal reduction therapy (SRT) at baseline, 88% no longer met the SRT indications after 24 weeks of treatment. Aficamten tablets were also well tolerated, with an incidence of adverse events comparable to that of the placebo group.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. Due to limitations in early screening methods, its prevalence is likely underestimated, currently estimated to be at least 1 in 200. Clinically, obstructive (resting and latent) HCM accounts for approximately two-thirds of cases, while non-obstructive HCM accounts for about one-third.

HCM can lead to exertional dyspnea, fatigue, chest pain, palpitations, syncope/pre-syncope, and exercise intolerance. Moreover, HCM is one of the leading causes of sudden cardiac death in adolescents and athletes. Disease-related fatal and disabling events can be attributed to sudden cardiac death, heart failure, and thromboembolic stroke. Sudden cardiac death is common in young patients aged 10–35 years, heart failure-related deaths occur more frequently in middle-aged patients, and strokes associated with HCM-related atrial fibrillation are more prevalent in elderly patients. The annual mortality rate among HCM patients treated in hospitals ranges from 2% to 4%.

Currently, the only approved myosin inhibitor in the same class is Mavacamten, developed by Bristol Myers Squibb. Other myosin inhibitors in development include HRS-1893 by Hengrui Pharmaceuticals.