The decade after rapid FDA approval ends long-term regulatory legend of drug intercept
While the pathway for any drug from laboratory research to commercialization takes years, intercepting drugs are now another example, that the market export of products can also be long and winding. The company is withdrawing the product nearly a decade after the interceptor of rare liver disease drugs.
The intercept said Thursday that its quit was voluntary. But the company pointed out that its decision follows the FDA request. Intercept also stated that regulators have placed clinically on all clinical trials involving active pharmaceutical ingredients in the product.
Ocaliva was developed for the treatment of primary cholangitis or PBC. This rare disease develops when the immune system mistakenly attacks the bile ducts of the liver, causing inflammation of the organs. For decades, standard treatment has been Ursodiol, an old gallstone dissolution drug that expanded its label to PBC in 1997. Obeticolic Acid, the main drug ingredient in Ocaliva, is an analog of bile acid found in humans. Oral small molecules bind to FXR and activate FXR, a receptor and intestinal receptor in the liver that play a role in regulating bile acids and inflammation.
Ursodiol is not suitable for all patients with PBC. The accelerated FDA approval received by Ocaliva in 2016 makes the pill a second-line treatment for people who respond to disease’s treatment to first-line URSODIOR. But intercept drugs have had a history of regulatory oversight of rocks since then. In 2021, the FDA added a black box warning to Ocaliva's label, marking the risk of severe liver complications in patients with cirrhosis.
Ocaliva's accelerated approval requires companies to conduct confirmation of clinical trials. Last year, the FDA rejected Intercept's application to convert the drug's condition into full approval in PBC. Soon after, the agency issued a safe communication to warn patients without cirrhosis of the risk of severe liver injury. In Europe where Ocaliva is sold by partner Advanz Pharma, the European Commission revoked the conditional marketing authorization for the product.
Intercept also stumbled upon efforts to extend Ocaliva to other signs. The FDA twice refused to cut off the drug as a treatment for fatty liver disease currently known as metabolic dysfunction-associated steatohepatitis (MASH). The restructuring was intercepted after a second rejection in 2023, and was then acquired by Alfasigma, a private company based in Italy.
PBC treatment options have expanded since Ocaliva first entered the market. Last year, the FDA awarded accelerated approval of two new PBC drugs: Iqirvo and Gilead Sciences'Livdelzi. These products bring different mechanisms of action to the disease. The regulatory decision covers the use of second-line treatment, making it comparable to Ocaliva. But there is no black box warning on the labels of ipsen and gilead drugs. Now that PBC patients can use safer treatments, the FDA clearly no longer believes that Ocaliva needs to remain on the market under accelerated approval.
The intercepted executives continue to be a US subsidiary of Alfasigma, U.S., who believe that overall clinical and real-world evidence supports Ocaliva in PBC. But the company has a conflict with the FDA about the matter.
“While our view on Ocaliva’s risk profile is different from the FDA’s perspective, we respect its requirements and have made this difficult decision to provide clear guidance for patients and prescribers,” Interpect U.S. President Vivek Devaraj said in a prepared statement.
Image: Sakramir, Getty Images
