The European Court of Justice in Luxembourg has granted a temporary suspension of the European Commission's decision to ban Ocaliva (obeticholic acid), a medication prescribed for primary biliary cholangitis (PBC). This rare liver disease progressively destroys bile ducts, potentially leading to liver failure and increasing the risk of liver cancer. The decision ensures that Ocaliva remains accessible to patients within the European Union, Iceland, Liechtenstein, and Norway, pending the outcome of a legal challenge filed by Advanz Pharma, the drug's manufacturer.
EMA Recommendation and Commission's Ban
The European Medicines Agency (EMA) had recently recommended withdrawing Ocaliva's marketing authorization following a review by its Committee for Medicinal Products for Human Use (CHMP). The review concluded that Ocaliva did not demonstrate significant benefit over a placebo in preventing disease progression or death in early-stage PBC patients. Consequently, the European Commission formally moved to ban the drug earlier this week.
Advanz Pharma's Response
Advanz Pharma swiftly responded by securing a temporary suspension of the ban from the EU's Court of Justice. Steffen Wagner, CEO of Advanz, stated, "We are committed to supporting patients and are pleased to have secured a temporary suspension of the EC decision. We will continue our efforts to help ensure longer-term continuity of supply of Ocaliva for all patients who need it."
Concerns over Treatment Alternatives
The potential removal of Ocaliva from the market had sparked protests, with patient advocacy groups arguing that there is no alternative second-line treatment licensed in Europe for PBC. Ocaliva is typically used when initial treatments, such as ursodeoxycholic acid, fail, stop working, or cause intolerable side effects. Advanz argues that revoking Ocaliva's authorization would leave thousands of PBC patients at increased risk of disease progression with limited treatment options.
Conditional Approval and Confirmatory Trials
Ocaliva received conditional marketing authorization in both the EU and the U.S. in 2016, contingent on further studies confirming its clinical benefits. This approval was based on data from the Phase 3 POISE trial, which demonstrated Ocaliva's superiority over placebo in normalizing blood markers of liver damage. However, the subsequent Phase 3b/4 COBALT clinical trial, designed to confirm these benefits, yielded less conclusive results.
COBALT Trial Data and Real-World Evidence
Results from the COBALT trial, published last month, indicated similar rates of death, liver transplant, and/or other serious liver-related events between patients on Ocaliva and placebo (28.6% vs. 28.9%). Advanz argues that the CHMP's decision focused too heavily on a single data analysis from COBALT, rather than considering real-world data gathered over seven years of clinical use. An analysis comparing COBALT participants assigned Ocaliva with an external group of untreated patients suggested a significant benefit, with a 61% lower risk of negative outcomes with Ocaliva (10.1% vs. 21.5%).
Ocaliva in the United States
In the U.S., where Ocaliva is marketed by Intercept Pharmaceuticals, regulators are reviewing an application for full approval. A decision is expected in October.
