▎WuXi AppTec Content Team Report

Today (October 17), the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China announced that the marketing application for injectable Sotatercept, submitted by MSD, has been accepted. Public information indicates that this is a"First-in-class" novel biologic activin signal inhibitor, the product has been approved for marketing by the U.S. FDA in March this year.Used for treatmentPulmonary Arterial Hypertension (PAH)。This therapy was previously rated by the industry media Evaluate as the 2024Potential BlockbusterOne of the therapies.

Screenshot source:CDE Official Website

PAH is a rare, progressive, life-threatening vascular disease,When the small arteries in the lungs become thickened and narrowed, it leads to increased pressure within these arteries, putting stress on the heart. PAHCan cause a significant increase in cardiac load, leading to limited physical activity, heart failure, and shortened life expectancy. The development of PAH involves three related processes, includingInflammation, Cell Proliferation, and Fibrosis, these processes play an important role in the thickening, narrowing, and stiffening of small pulmonary arteries, commonly referred to as "vascular remodeling." Currently approved PAH therapies primarily function as vasodilators to open blood vessels, but these treatments cannot reverse vascular remodeling caused by inflammation, proliferation, and fibrosis.

Sotatercept is a type IIA activin receptor (ActRIIA) fusion protein.. It fuses the modified extracellular domain of ActRIIA with the Fc portion of an antibody, which can block activin from binding to receptors on the cell membrane, therebyReduce Activin-Mediated Signaling。In preclinical studies, it can reverse the remodeling of the pulmonary artery wall and right ventricle.The product alsoMSD spent approximately $11.5 billion in 2021AcquisitionAcceleron PharmaKey therapies obtained.Previously, sotatercept had received the FDA's Breakthrough Therapy Designation for the treatment ofPulmonary Hypertension.

FDA ApprovalsotaterceptIs based on oneA randomized, double-blind, placebo-controlled pivotal Phase 3 clinical trialSTELLARThe Results。In March 2023, MSD announced the pivotalComplete Results of Phase 3 Clinical Trials, and the study results were also published simultaneously in The New England Journal of Medicine.。

The research results show that,In PAH patients, sotatercept increased the 6-minute walking distance (6MWD) by 40.8 meters from baseline after 24 weeks of treatment.In addition,Sotatercept also provided statistically significant and clinically meaningful improvements in 8 of the 9 secondary endpoints, including improvements in WHO functional class and pulmonary vascular resistance.Compared with placebo, at a median follow-up time of 32.7 weeks, it reduced the risk of clinical disease worsening or death by 84%.

MSD previously stated in a press release that these landmark results highlight the therapeutic potential of sotatercept and targeted cell signaling approaches associated with vascular hyperproliferation and pathological remodeling in the treatment of pulmonary arterial hypertension.

In September 2023, MSD announced aExploratory Post Hoc AnalysisResults. The results show that,Sotatercept can reduce the size of the right side of the heart, improve right ventricular function, and enhance hemodynamic indicators in PAH patients after 24 weeks of treatment.

In China, sotatercept was approved for clinical use in September last year, with the indication being pulmonary arterial hypertension. According to the Drug Clinical Trial Registration and Information Disclosure website, MSD had previously completed a trial evaluating healthy Chinese subjects.sotaterceptA Phase 1 clinical study on the safety, tolerability, and pharmacokinetics of a single dose. The acceptance of the product's marketing application in China marks a significant advancement in its development process, with the potential to benefit Chinese patients in the near future.

References:

[1] Official website of the Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Oct 17, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2] MSD Announces Phase III STELLAR Study Data for Investigational Drug Sotatercept.Retrieved Mar 7，2023. From https://mp.weixin.qq.com/s/viNQdtj1-LTjojrhAKWTIA

[3] Prescribing information. Retrieved March 26, 2024 https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761363s000lbl.pdf