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Intercept's Ocaliva Faces Setback as FDA Advisory Committee Recommends Against Full Approval for PBC

• The FDA's Gastrointestinal Drugs Advisory Committee (GIDAC) has voted against full approval of Intercept's Ocaliva for primary biliary cholangitis (PBC). • The vote raises concerns about Ocaliva's clinical benefit as a second-line therapy for PBC patients, despite eight years of real-world patient experience. • Intercept remains committed to working with the FDA to address concerns and seek full approval for Ocaliva, with a PDUFA date set for October 15, 2024. • Ocaliva, a farnesoid X receptor (FXR) agonist, is currently approved under accelerated approval based on reduction in alkaline phosphatase (ALP).

The Gastrointestinal Drugs Advisory Committee (GIDAC) of the U.S. Food and Drug Administration (FDA) has recommended against full approval of Intercept Pharmaceuticals' supplemental New Drug Application (sNDA) for Ocaliva (obeticholic acid, OCA) in treating primary biliary cholangitis (PBC). The sNDA aimed to secure full approval for Ocaliva and fulfill post-marketing requirements by confirming its clinical benefit for PBC patients. This decision casts doubt on the future of Ocaliva as a standard treatment for this rare liver disease.

Disappointment and Commitment

Paul Nitschmann, M.D., Senior Vice President of Regulatory Affairs at Intercept, expressed disappointment in the committee's decision, stating that the vote "does not accurately recognize the clinical benefit of OCALIVA as an important second-line therapy for patients living with PBC." Despite the setback, Intercept remains dedicated to collaborating with the FDA to address their concerns and advocate for patients.

Ocaliva's Role in PBC Treatment

Ocaliva, a farnesoid X receptor (FXR) agonist, has been available as a second-line therapy for PBC for eight years, accumulating over 42,000 years of collective real-world patient experience. It is currently approved for adult patients with PBC without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The drug's approval was based on a reduction in alkaline phosphatase (ALP) levels, a surrogate marker, under accelerated approval regulations. Continued approval is contingent upon verification and description of clinical benefit in confirmatory trials.

Primary Biliary Cholangitis (PBC)

PBC is a rare, progressive, chronic autoimmune disease affecting the bile ducts in the liver, predominantly in women over 40, with a prevalence of approximately one in 10,000. The condition leads to bile acid buildup, causing inflammation and scarring (fibrosis), which, if untreated, can progress to cirrhosis, liver transplant, or death.

Safety Information and Warnings

Ocaliva carries a boxed warning regarding hepatic decompensation and failure in PBC patients with cirrhosis. The drug is contraindicated in patients with decompensated cirrhosis, a prior decompensation event, or compensated cirrhosis with evidence of portal hypertension. Adverse reactions, including severe pruritus and reductions in HDL-C, have been reported. Drug interactions with bile acid binding resins, warfarin, and CYP1A2 substrates necessitate careful monitoring and dose adjustments.

Regulatory Outlook

While the FDA will consider the advisory committee's vote, it is not bound by it. The final decision is expected by the Prescription Drug User Fee Act (PDUFA) target action date of October 15, 2024. The pharmaceutical community awaits the FDA's final verdict, which will significantly impact the treatment landscape for PBC patients.
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Reference News

[1]
Company Statement on FDA Advisory Committee Meeting - BioSpace
biospace.com · Sep 14, 2024

FDA's GIDAC discussed Intercept's sNDA for OCALIVA for PBC treatment; Intercept disappointed by the committee's vote, em...

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