Advanz gets suspension of decision to revoke Ocaliva EU approval
Regulatory decision made last week based on CHMP recommendation
Advanz Pharma has secured a temporary suspension of a decision by the European Commission (EC) to revoke conditional approval of Ocaliva (obeticholic acid) for the treatment of certain people with primary biliary cholangitis (PBC).
This means that the therapy will continue to be available for eligible patients in the European Union, as well as Iceland, Liechtenstein, and Norway.
“We are committed to supporting patients and are pleased to have secured a temporary suspension of the EC decision,” Steffen Wagner, CEO of Advanz, which markets the therapy in Europe, said in a company press release. “We will continue our efforts to help ensure longer-term continuity of supply of Ocaliva for all patients who need it.”
Ocaliva was conditionally approved in both the EU and the U.S. in 2016 as a second-line PBC treatment for patients who have responded inadequately to or cannot tolerate the first-line therapy ursodeoxycholic acid.
A conditional, or accelerated, approval is granted based on early clinical trial evidence that support a treatment’s therapeutic potential. However, conversion to a full approval requires additional trial data to confirm the therapy’s safety and efficacy.
Advanz announced last week that the EC had revoked Ocaliva’s conditional authorization on the basis of a June recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). That recommendation, for the revocation of the conditional approval, noted that available data did not support Ocaliva’s clinical benefits, thus failing to meet the requirements for continued marketing authorization.
Advanz CEO says company ‘strongly’ disagrees with EC decision
In its press release announcing the EC decision, Advanz had noted a potential negative effect for those prescribed the medication, stating that revocation would “[leave] thousands of patients with PBC who are responding well to Ocaliva at increased risk of disease progression with limited treatment options.”
Wagner said: “We strongly disagree with the European Commission’s decision to withdraw the conditional marketing [authorization] for Ocaliva … until now the only approved and available second-line treatment option in Europe.
“The removal of Ocaliva could have a profoundly negative impact on the lives of the thousands of patients with PBC across Europe who have benefitted from this important treatment over many years.”
Advanz, in opposition of the decision, started looking for ways to ensure existing and new patients would have continued access to the therapy. Now, the company was able to secure a temporary pause on the EC decision by order of the president of the EU’s General Court.
“This enables immediate continuity of supply until the next decision by the General Court,” Wagner now said.
In the U.S., where Ocaliva is marketed by Intercept Pharmaceuticals, regulators are reviewing an application from the company seeking conversion of its current conditional approval to a full approval. A decision in that country is expected in October.
Company says real-world data, trial results support Ocaliva benefits
Ocaliva works by modulating the farnesoid X receptor, a protein involved in pathways implicated in PBC, a rare disease characterized by inflammation in the ducts that carry the digestive fluid bile from the liver to the intestines.
The therapy’s conditional approvals were based largely on biomarker data from the Phase 3 POISE trial (NCT01473524), which demonstrated that Ocaliva was better than a placebo for normalizing blood markers of liver damage.
The confirmatory Phase 3b/4 COBALT clinical trial (NCT02308111) was launched to confirm Ocaliva’s benefits and subsequently support a full approval, should the results be positive.
It was designed to test the therapy’s effects on long-term clinical outcomes against a placebo in hundreds of adults with high-risk PBC based on biomarker levels linked to more advanced disease and an elevated risk of disease progression.
Advanz doesn’t believe that the CHMP adequately considered all of the available evidence supporting Ocaliva’s safety and efficacy in PBC. According to the company, the committee mainly focused on a single data analysis from COBALT, rather than also considering the real-world data gathered over the last seven years of the treatment’s clinical use.
Combined clinical trial and real-world data offer important evidence of the potential long-term clinical benefit of treatment with [Ocaliva]. … [The] findings [together] … build on the totality of evidence providing greater insight into the impact of [Ocaliva] on clinical outcomes in patients living with PBC.
COBALT results published last month indicated that rates of death, liver transplant, and/or other serious liver-related events — the study’s primary goal — were similar between patients on Ocaliva and the placebo (28.6% vs. 28.9%).
However, there were some limitations to the trial. Among them was that many individuals assigned to the placebo chose to discontinue their participation early to instead receive the commercial therapy. These patients still had to be considered as part of the placebo group in trial analyses, according to Advanz.
In anticipation of this problem, a prespecified analysis was planned to compare data from COBALT participants assigned Ocaliva with those from an external group of untreated patients from a U.S. healthcare claims database who had similar characteristics to the study population.
Such analyses suggested a significant and clinically meaningful benefit of Ocaliva, with a significantly lower proportion of patients on the therapy meeting the primary goal (10.1% vs. 21.5% of the external group). This reflected a 61% lower risk of negative outcomes with Ocaliva.
“Combined clinical trial and real-world data offer important evidence of the potential long-term clinical benefit of treatment with [Ocaliva],” Sangeeta Sawhney, MD, senior vice president and head of U.S. research and development for Intercept, said in a separate company press release. “Findings from this study are consistent with other real-world analyses and build on the totality of evidence providing greater insight into the impact of [Ocaliva] on clinical outcomes in patients living with PBC.”
Advanz recommended that patients now taking Ocaliva consult with their treating physicians should they have any questions about the therapy’s use.
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