Elafibranor, now Iqirvo, wins FDA accelerated approval for PBC

Second-line therapy would be first to win FDA approval since 2016

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ipsen’s elafibranor as a second-line treatment for primary biliary cholangitis (PBC).

The oral therapy, which will be sold under the brand name Iqirvo, is indicated for use in combination with the first-line therapy ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy (on its own) in those who can’t tolerate UDCA.

“For a significant number of people living with PBC, available treatments do not control the condition and may exacerbate symptoms of PBC,” Christelle Huguet, PhD, Ipsen executive vice president and head of research and development, said in a company press release. “Left unmanaged, PBC can progress, leading to liver failure and in some cases, the need for a liver transplant.”

The decision makes Iqirvo the first new therapy for PBC to win FDA approval since the clearance of Ocaliva (obeticholic acid) as a second-line therapy in 2016.

Iqirvo is “much-needed treatment option and the first new medicine for PBC in nearly a decade,” Huguet said.

European approval decisions pending

FDA’s accelerated approval pathway allows promising therapies to be marketed based on early clinical evidence that they’re probably effective. As a condition of accelerated approval, drug developers have to conduct further testing to prove the therapy provides clinical benefits as expected.

Iqirvo is available in 80 mg tablets, and the approved dosage is 80 mg once daily taken with or without food. To support patients accessing the newly authorized therapy, which will be immediately available in the U.S., Ipsen offers a support program, Ipsen Cares, which can be accessed online or by phone at 1-866-435-5677.

Iqirvo is also up for approval in the European Union and the U.K., with decisions expected in the second half of 2024.

PBC is an autoimmune disorder characterized by chronic inflammation in the bile ducts, a series of tubes that carry the digestive fluid bile out of the liver and to the intestines. This can lead to damage and scarring in the liver.

Originally developed by Genfit, Iqirvo works to modulate the activity of proteins called PPARs, which are involved in regulating gene activity related to processes that contribute to liver damage in PBC, including inflammation and scarring. The treatment is the first PPAR-targeting medication to be approved for PBC.

Carol Roberts, executive president of patient advocacy organization PBCers, said that “new treatment options are important to meet the current needs of people living with PBC.”

Elafibranor Phase 3 clinical trial met goals

Iqirvo’s accelerated approval was based on data from the ongoing Phase 3 ELATIVE clinical trial (NCT04526665), which tested the therapy against a placebo in 161 adults who didn’t respond to or couldn’t tolerate UDCA.

Top-line results demonstrated Iqirvo was better than a placebo at reducing levels of liver damage markers, including alkaline phosphatase (ALP) and bilirubin, after one year, meeting the study’s main goal.

“Iqirvo demonstrated statistically significant improvements in biochemical response compared to UDCA alone,” Huguet said.

Recently presented data from ELATIVE showed that Iqirvo also outperformed a placebo at improving patients’ sleep and easing itch — a common PBC symptom that occurs when built-up bile spills out of the liver into the bloodstream.

“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 Kris Kowdley, MD, one of ELATIVE’s primary investigators and director of 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.”

Iqirvo’s common side effects include weight gain, abdominal pain, nausea, vomiting, and diarrhea. The therapy also may cause allergic reactions, joint or muscle pain, and bone fractures.

The therapy is not recommended for use in patients who are pregnant or breastfeeding. Individuals who have the capacity to become pregnant need to use an effective form of non-hormonal contraception while taking Iqirvo, as the therapy will make hormonal contraceptives such as birth control pills less effective.

“This approval is a source of pride for all GENFIT employees,” Pascal Prigent, CEO of Genfit, said in a press release from that company. “We took elafibranor (Iqirvo) all the way from drug discovery to the end of Phase 3 and now, thanks to our partnership with Ipsen, it will be made available to healthcare providers in the US and ultimately provide patients with a valuable therapeutic alternative.”

Iqirvo’s effects on long-term liver health and survival in people with PBC remain unproven, though another Phase 3 trial called ELFIDENCE (NCT06016842) is evaluating how the treatment impacts survival in PBC patients. ELFIDENCE is actively recruiting participants at sites in the U.S., Europe, and South Korea.

An ongoing Phase 2 study called ELMWOOD (NCT05627362) is testing the therapy in adults with primary sclerosing cholangitis (PSC), which like PBC is a chronic disorder marked by bile duct inflammation. That study is recruiting at sites across the U.S., Canada, and Europe.