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The FDA granted accelerated approval to oral elafibranor (Iqirvo) for treating primary biliary cholangitis (PBC) in adults, drugmaker on Monday.

A first-in-class dual peroxisome proliferator-activated receptor (PPAR) agonist, elafibranor is indicated in combination with ursodeoxycholic acid (UDCA) for patients with an inadequate response to UDCA, or as monotherapy for those unable to tolerate the standard first-line therapy. The drug is not recommended for patients with decompensated cirrhosis.

PBC is a rare, chronic cholestatic liver disease that left untreated can progress to cirrhosis, require liver transplantation, and result in premature death.

Support for elafibranor's accelerated approval came from ELATIVE, a randomized multicenter trial of 161 patients with PBC, most of whom (95%) had an inadequate response to UDCA.

For the study's primary endpoint, 51% of patients treated with an 80-mg once-daily dose of elafibranor achieved a biochemical response indicative of a reduction in cholestasis at week 52, as compared with 4% of placebo recipients (P<0.0001). Biochemical response was defined as an alkaline phosphatase (ALP) level less than 1.67 times the upper limit of normal, an ALP decrease from baseline of at least 15%, and total bilirubin no higher than the upper limit of normal.

"Data from the pivotal phase III ELATIVE clinical trial demonstrated that Iqirvo is an effective second-line treatment for patients with PBC with favorable benefit and risk data," said primary investigator Kris Kowdley, MD, director at Liver Institute Northwest in Seattle. "The approval of Iqirvo will allow healthcare providers in the U.S. to address an unmet need with the potential to significantly reduce ALP levels for our patients with PBC."

Treatment led to rapid reductions in ALP, and a key secondary endpoint showed ALP normalization in 15% of patients on elafibranor at week 52 versus none of the patients on placebo (P=0.002).

While the mechanism of action of elafibranor is not well understood, the drug has been shown to inhibit bile acid synthesis through activation of PPAR-alpha and PPAR-delta.

As the drug has not shown a survival improvement or reduction in liver decompensation events, demonstration of further clinical benefit in confirmatory trials may be required for continued approval.

Common adverse events in ELATIVE included weight gain (23% with elafibranor vs 21% with placebo), diarrhea (11% vs 9%, respectively), abdominal pain (11% vs 6%), nausea (11% vs 6%), and vomiting (11% vs 2%).

also includes warnings and precautions about myalgia, myopathy, and rhabdomyolysis; fractures; adverse effects on fetal and newborn development; drug-induced liver injury; hypersensitivity reactions; and biliary obstruction. Drug interactions may occur with hormonal contraceptives, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, rifampin, and bile acid sequestrants.

Elafibranor is available for prescribing immediately in the U.S., Ipsen said.

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