The European Commission, following the advice of the Committee for Medicinal Products for Human Use (CHMP), has revoked the conditional marketing authorization of Advanz Pharma's Ocaliva in Europe for second-line treatment of patients with Primary Biliary Cholangitis (PBC).
Ocaliva, a farnesoid X receptor agonist, was the only approved and available second-line treatment PBC option in Europe, having received conditional approval in 2016.
Back in June, CHMP had recommended that the medicine’s marketing authorization be revoked, claiming that Ocaliva's benefits no longer outweighed its risks. CHMP pointed to Study 747-302 (COBALT), which the committee said failed to show that Ocaliva was more effective than placebo in terms of the number of patients whose disease worsened or who died, both in the overall population and in a group of patients with early stage PBC. Additionally, the committee said that
data from supportive studies and real-world data were not sufficient to counterbalance the negative results of the trial.
Advanz Pharma, however, says that the CHMP recommendation "did not adequately consider the totality of available data supporting the efficacy and safety of Ocaliva in PBC, in particular the wealth of positive real-world evidence gathered from more than seven years of clinical use representing over 47,000 patient-years of treatment experience." Instead, according to Advanz, CHMP relied on one analysis based on the single, randomized placebo-controlled trial (Study 747-302).
The drug's fate on the U.S. market is still hanging in the balance. In the U.S., Ocaliva is marketed by Intercept Pharma, where it was granted accelerated approval by the FDA in 2016 to treat adult PBC patients without cirrhosis or with compensated cirrhosis. An FDA AdComm is schedule to meet on September 13 to determine if Ocaliva has fulfilled the accelerated approval postmarketing requirements specified in its accelerated approval.
PBC is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent in women over the age of 40. The disease causes bile acid to build up in the liver, resulting in inflammation and scarring, which can lead to cirrhosis, a liver transplant or death.
