FDA to decide on full approval for Ocaliva in treating adults with PBC

Decision, due by mid-October, supported by real-world therapy use

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) agreed to review an application seeking full and formal approval of Ocaliva (obeticholic acid) as a treatment for adults with primary biliary cholangitis (PBC), the company marketing the therapy, Intercept Pharmaceuticals, reports.

Ocaliva was granted accelerated approval by the FDA in 2016 to treat adult PBC patients without cirrhosis (irreversible liver scarring) or with compensated cirrhosis — where the liver is scarred but still functional — but no evidence of portal hypertension. Portal hypertension is high blood pressure in a major vein that carries blood from the gastrointestinal tract to the liver.

The treatment is indicated for use in combination with ursodeoxycholic acid (UDCA) in patients who don’t respond to UDCA alone, or it can be a sole therapy for those unable to tolerate UDCA. UDCA, also called ursodiol and marketed as Urso and Actigall, is the first-line PBC therapy.

In accelerated approval, the FDA allows pharmaceutical companies to bring a drug to market based on clinical data showing the therapy is likely to be effective. To achieve full approval, drug developers are required to conduct additional testing to prove therapy effectiveness more conclusively.

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Ocaliva is designed to ease bile duct inflammation, increase bile flow

Intercept’s new supplemental new drug application, or sNDA, aims to fulfill these requirements and move Ocaliva to a traditional approval. The FDA is expected to decide on the application on or before Oct. 15.

The regulatory agency also is planning to have an advisory committee meeting, where a group of outside experts are asked to review the application in detail and offer their insights.

“We are pleased that the FDA has filed the submission and look forward to continued, constructive interactions with the agency, including discussing our precedent-setting application during the forthcoming Advisory Committee meeting,” Paul Nitschmann, MD, senior vice president of regulatory affairs at Intercept, a wholly owned subsidiary of Alfasigma, said in a company press release.

PBC is a form of cholangitis, or inflammation of the bile ducts, a series of tubes that carry the digestive fluid bile from the liver to the intestines.

Ocaliva is designed to reduce bile duct inflammation and increase bile flow out of the liver by activating a bile-regulating liver protein called the farnesoid X receptor.

Accelerated approval was based mainly on data from a Phase 3 POISE (NCT01473524) clinical trial, which tested Ocaliva against a placebo in more than 200 PBC patients. Results indicated that a significantly greater proportion of patients given the therapy had a normalization of liver damage markers than those on a placebo (46% vs. 10%).

Real-world use of Ocaliva supports its effectiveness in adults with PBC

The sNDA also includes data from two placebo-controlled Phase 4 trials: COBALT (NCT02308111) and Study 401 (NCT03633227).

The COBALT study aimed to test Ocaliva against a placebo in more than 300 PBC patients. But the trial was stopped early because it was deemed infeasible to run a placebo-controlled study for PBC, a serious rare disease, when the therapy being tested was already commercially available to patients.

Study 401, which aimed to assess Ocaliva’s effects in PBC patients with moderate to severe liver impairment, also was terminated early. This was due to a label update contraindicating the therapy’s use in patients with decompensated cirrhosis, a prior decompensation event, or compensated cirrhosis with evidence of portal hypertension.

As such, Intercept initiated multiple real-world studies, including HEROES PBC (NCT05292872). Data from this large and observational study showed that Ocaliva treatment was associated with a statistically significant and clinically meaningful reduction in all-cause death, the need for a liver transplant, or hospitalization for liver decompensation.

“The sNDA data submission asserted that, with more than seven years on the market and more than 40,000 patient-years of post-marketing experience in PBC, Ocaliva is the only second-line therapy that has multiple published analyses of registry data and real-world evidence showing significant effect on transplant-free and decompensation-free survival in people living with PBC,” Nitschmann said.