On October 11, the NMPA issued 43 "notification documents" without drug approval numbers, including Fudan-Zhangjiang's obeticholic acid tablets. On October 13, Fudan-Zhangjiang announced that its subsidiary had received a "Drug Marketing Application Disapproval Notice" from the National Medical Products Administration. The previously submitted application for obeticholic acid tablets intended to treat primary biliary cholangitis (PBC) was not approved.

The main reason for the regulatory agency's disapproval was that the imported original drug for Fudan-Zhangjiang's obeticholic acid tablets had "crashed" overseas due to safety issues and was withdrawn from European and American markets.

**Original Drug Withdrawn from European and American Markets Due to Safety Issues**

Primary biliary cholangitis (PBC) is a rare, progressive, chronic autoimmune disease, formerly known as primary biliary cirrhosis, most prevalent in women over 40 years old (approximately 1 in 10,000). PBC causes bile acid accumulation in the liver, leading to inflammation and scar formation (fibrosis). Without timely treatment, it may result in bile duct destruction, cholestasis, liver fibrosis, and potentially progress to cirrhosis and liver failure.

Public information shows that the original obeticholic acid drug (brand name: Ocaliva) is a farnesoid X receptor (FXR) agonist developed by Intercept Pharmaceuticals. Industry data indicates that obeticholic acid's global sales showed steady growth from 2016-2021 before stabilizing: approximately $250 million in 2019; $310 million in 2020, a 25.3% year-over-year increase; peaking at $363 million in 2021, then stabilizing around $300 million in subsequent years.

Since its market launch, the drug's clinical risk-benefit ratio has been consistently questioned. In 2017, just over a year after Ocaliva's approval, the FDA's adverse event reporting system had already received multiple reports of Ocaliva-related deaths and serious liver injury. In 2018, the FDA added a black box warning to obeticholic acid's labeling, emphasizing the risk of hepatic decompensation and liver failure in patients with moderate and severe hepatic impairment.

In October 2023, the European Medicines Agency (EMA) assessed that existing data could not confirm obeticholic acid's clinical benefits and recommended revoking its marketing authorization. In September 2024, the European Commission made the decision to withdraw from the European market, followed by the FDA's refusal to convert Ocaliva to full approval in November, essentially foreshadowing Ocaliva's withdrawal outcome.

On September 11, 2025, Intercept Pharmaceuticals announced that at the request of the US FDA, it would voluntarily withdraw the primary biliary cholangitis (PBC) treatment drug OCALIVA (obeticholic acid) from the US market. Simultaneously, the FDA suspended all clinical trials involving obeticholic acid.

**Domestic Generic Drugs Affected**

With the exposure of the original drug's safety risks and successive withdrawals from European and American markets, its domestic generic prospects also face tremendous uncertainty.

Fudan-Zhangjiang explained in its announcement that its submitted obeticholic acid tablets, as a domestic generic drug, could not receive regular approval because the reference preparation (original drug) had not obtained regular approval abroad. Given that post-marketing studies of the original drug clearly showed lack of confirmed benefits and the presence of serious risks, current data cannot adequately support the drug's approval according to Class 3 generic drug regular approval technical requirements.

The announcement also revealed that Fudan-Zhangjiang has cumulatively invested approximately 125 million yuan in research and development for the obeticholic acid tablets project.

Currently, no obeticholic acid products are marketed in China. Besides Fudan-Zhangjiang, multiple pharmaceutical companies have encountered setbacks in their obeticholic acid generic drug development: Hengrui Medicine submitted a marketing application in December 2020 and received acceptance, but approval remains pending; in February 2024, Chia Tai Tianqing's obeticholic acid tablets submitted a marketing application and received acceptance, but notification documents from September 1 this year show it was not approved.