PBC therapy Ocaliva pulled from EU market with court decision
Ruling puts into effect EC's withdrawal of treatment's conditional approval
Ocaliva (obeticholic acid) is no longer available to treat primary biliary cholangitis (PBC) across the European Union (EU), with an earlier decision to revoke its conditional marketing authorization now taking effect.
In September, the European Commission (EC) announced it would follow a recommendation by a European Medicines Agency (EMA) committee, which found that available data did not support Ocaliva’s clinical benefits and its marking rights should be withdrawn.
About a week later, however, Advanz Pharma, which markets the therapy in regions outside the U.S., secured a temporary suspension of that ruling from EU’s General Court.
The court now has decided not to extend the suspension, putting that the EC’s revocation of marketing authorization into immediate effect across the EU, as well as in Iceland, Liechtenstein, and Norway.
Patients in Europe might continue treatment via special access programs
“We are very disappointed by the General Court’s decision,” Steffen Wagner, Advanz’s CEO, said in a company press release. “Ocaliva is a much-needed treatment option for thousands of patients with PBC in Europe.”
Advanz argues that the court only considered the potential of the EC’s decision to seriously affect the company. It did not account for its potential impact on patients, or on the “overall validity” of the decision by EU’s governing body in the first place.
That EC decision and its validity are part of an ongoing annulment procedure at the General Court, the company stated, with a ruling expected next year.
The EMA, it added, has indicated that Ocaliva still may be made available to patients already using the therapy through compassionate use or named patient programs, provided local laws and regulations are adhered to. These programs provide people without effective treatment options access to therapies not approved in their country.
“Advanz Pharma disagrees with the EC revocation decision and remains committed to supporting patients with PBC and is in discussion with relevant national agencies to enable continued access for patients who rely on this medicine,” Wagner noted.
Ocaliva is designed to lower damaging bile acid levels in the liver
PBC is characterized by chronic cholangitis, or inflammation in the series of tubes that transport the digestive fluid bile from the liver to the intestines. Inflammation can damage the bile ducts and cause bile to accumulate in the liver, which can seriously harm the organ over time, and lead to disease symptoms of abdominal pain, fatigue, fever, and jaundice (yellowing of the skin and eyes).
Ocaliva works by activating the farnesoid X receptor, which controls bile acid production, and it is expected to help lower bile acid levels in the liver.
Ocaliva was conditionally approved in both the EU and U.S. in 2016 as a second-line PBC treatment for adults who respond inadequately to, or cannot tolerate, first-line treatment with ursodeoxycholic acid. Conditional approval allows a therapy to be marketed, but regulators await more clinical data to back a full approval.
The treatment also has faced regulatory hurdles in the U.S., where it is marketed by Intercept Pharmaceuticals, its developer. The company applied to the U.S. Food and Drug Administration (FDA) earlier this year, seeking to convert Ocaliva’s conditional authorization to a full approval. But the regulatory body recently rejected the application, indicating it could not grant such approval based on currently available data.
Rather, the FDA noted that it was still considering safety data from the Phase 4 COBALT clinical trial (NCT02308111) and other studies. The therapy remains available to patients in the U.S. under its conditional marketing authorization.
Initial approvals based on Phase 3 trial data, confirmatory studies less clear
Ocaliva’s conditional approvals were backed by data from the Phase 3 POISE trial (NCT01473524), which showed that the therapy was better than a placebo at normalizing blood markers of liver damage.
Two placebo-controlled confirmatory Phase 4 trials — COBALT and Study 401 (NCT03633227) — were intended to support applications for Ocaliva’s full approval. Both studies, however, were stopped early.
Data from COBALT showed similar rates of death and serious liver-related events between the Ocaliva and placebo patient groups, failing to meet the study’s main goal.
Additional analyses, however, indicated that the therapy lowered the risk of those events by 61% compared with real-world data from an external group of untreated patients.
Advanz previously indicated that the EMA committee, in its opinion, failed to adequately considered all the available clinical data supporting Ocaliva’s use in PBC patients when it made its negative recommendation to the EC.
“Ocaliva has a different mechanism of action from other treatments and is backed by a wealth of positive real-world evidence, gathered from more than seven years of clinical use,” Wagner said. “Without Ocaliva, patients could be at increased risk of disease progression, including serious liver harm, liver transplantation or death.”
The company recommends that patients affected by the recent General Court decision consult with their doctors if they have any questions.
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