Group 1 - Fudan Zhangjiang Biopharmaceutical Co., Ltd. announced that its subsidiary, Taizhou Fudan Zhangjiang Pharmaceutical Co., Ltd., received a notification from the National Medical Products Administration stating that the application for the drug Ocaliva (Obeticholic Acid) for the treatment of primary biliary cholangitis (PBC) was not approved due to non-compliance with drug registration requirements [1] - The drug is a generic version of a conditionally approved overseas drug, and the original reference formulation has not received regular approval abroad, leading to concerns about the risk-benefit profile of the drug [1] - The company has invested approximately RMB 125 million in the research and development of this drug as of the announcement date [1] Group 2 - Ocaliva, developed by Intercept Pharmaceuticals, is a Farnesoid X receptor (FXR) agonist that received accelerated approval from the FDA in May 2016 for PBC patients who are intolerant to or unresponsive to Ursodeoxycholic acid (UDCA) [2] - On September 11, 2023, Intercept Pharmaceuticals voluntarily withdrew Ocaliva from the U.S. market at the request of the FDA, which also suspended all clinical trials involving the drug [2]

Core Viewpoint - Fudan Zhangjiang (688505.SH) announced that its subsidiary, Taizhou Fudan Zhangjiang Pharmaceutical Co., Ltd., received a notice from the National Medical Products Administration stating that the application for the marketing authorization of Ocaliva (Obeticholic Acid Tablets) for the treatment of primary biliary cholangitis (PBC) was not approved due to non-compliance with drug registration requirements [1] Group 1: Drug Approval and Market Impact - The primary reason for the rejection of the marketing application is the safety issues associated with the original drug, which led to its withdrawal from the European and American markets [1][2] - Fudan Zhangjiang has invested approximately 125 million yuan in the development of Obeticholic Acid Tablets, but the company stated that the rejection will not have a significant impact on its current financial status [1][3] Group 2: Original Drug Background - The original drug, Ocaliva, developed by Intercept Pharmaceuticals, was first approved by the FDA in May 2016 and received conditional approval in Europe in December 2016 [2] - The global sales of Ocaliva showed steady growth from 2016 to 2021, reaching approximately 363 million USD in 2021, but stabilized around 300 million USD in subsequent years [2] Group 3: Safety Concerns and Regulatory Actions - Since 2017, there have been multiple safety alerts regarding Ocaliva, including reports of severe liver damage and even death, leading to the FDA placing a "black box warning" on the drug [3] - In October 2023, the European Medicines Agency recommended the withdrawal of Ocaliva's marketing authorization, which was officially revoked in September 2024 [3] Group 4: Domestic Generic Drug Landscape - Currently, there are no approved domestic versions of Obeticholic Acid, and the safety risks associated with the original drug have created significant uncertainty for its generic prospects in China [4][5] - Several domestic pharmaceutical companies, including Hengrui Medicine and Zai Lab, are also facing setbacks in their applications for Obeticholic Acid generics [5][6]

Takeda Pharmaceutical - Rhonda Pacheco will become the head of Takeda's U.S. business unit on September 29, succeeding Julie Kim, who will transition to CEO in June 2026 [2] Maze Therapeutics - Shares of Maze Therapeutics increased by over 50% following positive Phase 1 data for its oral medicine MZE782, which showed good tolerance and exceeded expectations for amino acid levels [2] - Maze Therapeutics raised $150 million in a private stock offering alongside the positive results [2] Intercept Pharmaceuticals - Intercept Pharmaceuticals will withdraw its liver disease drug Ocaliva from the U.S. market at the FDA's request, which has also suspended all clinical trials for the drug due to safety concerns [2] - Ocaliva has faced scrutiny since its approval in 2016, with a black box warning added in 2018 and ongoing issues with approval for other indications [2] Soleno Therapeutics - Soleno Therapeutics' stock fell nearly 20% after a patient death was reported to the FDA, although the treating physician did not believe the drug Vykat was related to the incident [2] - The company has seen its shares lose about one-third of their value since a report by Scorpion Capital raised safety concerns about Vykat, the first approved drug for Prader-Willi syndrome [2]