China's NMPA Accepts NDA for Novel Brain Cytoprotectant Y-3 for Acute Ischemic Stroke Treatment
核心洞察
China Medical System Holdings announced that China's NMPA has accepted the New Drug Application for Y-3 for Injection (Loberamisal), a first-in-class brain cytoprotectant targeting PSD95-nNOS (搜索) and MPO (搜索) for acute ischemic stroke treatment.
Phase II clinical trials demonstrated that patients receiving Y-3 40mg daily achieved a 16% higher rate of excellent functional outcomes (mRS 0-1) at 90 days compared to placebo, with Phase III trials meeting primary efficacy endpoints across nearly 1,000 patients.
The drug addresses a significant unmet medical need in China, where approximately 3.94 million new stroke cases occur annually, with ischemic stroke accounting for 72% of cases and over 28 million existing stroke patients nationwide.
China Medical System Holdings Limited announced on December 11, 2025, that the National Medical Products Administration of China has accepted the New Drug Application for Y-3 for Injection, a Class 1 innovative brain cytoprotectant indicated for acute ischemic stroke treatment. The drug, with the proposed generic name Loberamisal for Injection, represents the world's first brain cytoprotectant developed based on the dual targets PSD95-nNOS (搜索) and MPO (搜索).
Novel Multi-Target Mechanism of Action
Y-3 for Injection operates through a unique multi-target approach that addresses the complex pathological processes of acute ischemic stroke. The drug uncouples PSD95-nNOS (搜索), inhibits MPO (搜索) activity, and enhances α2-GABAA receptor activity, a subtype with antidepressant and anxiolytic effects. This multi-target, highly selective synergistic mechanism enables the drug to act on multiple key pathological processes of the ischemic cascade, potentially achieving simultaneous stroke treatment and prevention of post-stroke depression and anxiety.
Strong Clinical Trial Results
The Phase II clinical trial results, presented at the 10th European Stroke Organisation Conference in 2024, demonstrated significant efficacy across multiple dosing regimens. Among patients with ischemic stroke within 48 hours of onset, the Y-3 groups showed substantially higher proportions of patients achieving excellent functional outcomes (mRS 0-1) at 90 days compared to placebo: 67.8% versus 60.7% for the 20mg group, 76.7% versus 60.7% for the 40mg group, and 70.0% versus 60.7% for the 60mg group. The 40mg daily dose demonstrated a particularly notable rate difference of 16% compared to placebo.
The Phase III clinical trial, led by Beijing Tiantan Hospital at Capital Medical University, enrolled nearly 1,000 patients with acute ischemic stroke within 48 hours of onset across approximately 40 research centers nationwide. The study met its primary efficacy endpoint, with patients achieving significant clinical benefits and maintaining an overall favorable safety profile. The drug showed comparable safety to placebo in acute ischemic stroke patients, exhibiting good tolerability.
Addressing Critical Medical Need
The approval comes at a crucial time for China's healthcare system, which faces an enormous stroke burden. According to the Guideline for Prevention and Treatment of Cerebrovascular Disease (2024 Edition) issued by the National Health Commission, approximately 3.94 million new stroke cases occur in China annually, representing one-third of global new cases. Ischemic stroke accounts for about 72% of these cases, with over 2.8 million new cases annually, and the total number of existing stroke patients in China has exceeded 28 million.
Data from China's cause-of-death monitoring in 2021 reveals that stroke-related deaths accounted for 23% of national total deaths. The disease burden of stroke-related disabilities has continued to increase over the past three decades, and with accelerating population aging, the pressure of stroke prevention and control is expected to intensify further.
Comprehensive Therapeutic Potential
Beyond acute stroke treatment, Y-3 for Injection addresses common post-stroke complications. Post-stroke depression and anxiety are prevalent complications with incidence rates of approximately 30% and 25% respectively. These conditions can hinder neurological function recovery, increase death risk, and severely affect patient prognosis. The drug's potential to simultaneously address stroke treatment and prevent post-stroke depression and anxiety represents a significant therapeutic advancement.
Strategic Partnership and Market Position
China Medical System Holdings obtained exclusive promotion rights for Y-3 for Injection in mainland China, Hong Kong, and Macau through a permanent collaboration agreement with Neurodawn Pharmaceutical Co., Ltd., signed on August 24, 2023. The addition of Y-3 for Injection strengthens CMS's Central Nervous System portfolio, which includes marketed products such as VALTOCO (搜索) (Diazepam Nasal Spray), Deanxit (Flupentixol and Melitracen Tablets), and ZUNVEYL (Benzgalantamine Gluconate Enteric-coated Tablets), currently under NDA review.
The company plans to leverage its successful commercialization experience and compliant operation system to accelerate the accessibility of this innovative therapy. Key study results are planned for presentation at international academic conferences, with full study publication expected in international academic journals.