FDA approves Ipsen’s Iqirvo ‘to address unmet need’ in primary biliary cholangitis
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The FDA granted accelerated approval to Ipsen Pharma’s Iqirvo 80 mg, a first-in-class oral, once-daily peroxisome proliferator-activated receptor agonist for the treatment of primary biliary cholangitis, according to a company release.
Originally given breakthrough therapy designation in 2019, Iqirvo (elafibranor, Ipsen/Genfit), is now indicated as second-line therapy in combination with ursodeoxycholic acid (UDCA) for adult patients with inadequate response to UDCA, or as monotherapy in those who are intolerant to UDCA.
The FDA based its decision on Iqirvo’s reduction in alkaline phosphatase levels, which were “sustained through week 52” with rapid response “seen as early as week 4” in the randomized double-blind, placebo-controlled, phase 3 ELATIVE trial, intended to assess the efficacy and safety of once-daily Iqirvo 80 mg plus UDCA (n=108) vs. placebo plus UDCA (n=53).
“Data from the pivotal phase 3 ELATIVE clinical trial demonstrated that Iqirvo is an effective second-line treatment for patients with PBC with favorable benefit and risk data,” Kris Kowdley, MD, director at Liver Institute Northwest in Washington and a primary investigator on the ELATIVE study, said in an Ipsen press release. “The approval of Iqirvo will allow health care providers in the U.S. to address an unmet need with the potential to significantly reduce ALP levels for our patients with PBC.”
According to the 52-week results, 13 times more patients treated with Iqirvo plus UDCA achieved the composite primary endpoint of biochemical response compared with placebo plus UDCA (51% vs. 4%), with a treatment difference of 47%. Further, the secondary endpoint of ALP normalization was achieved in 15% of patients treated with Iqirvo vs. none who received placebo.
During the recent EASL Congress, researchers reported that Iqirvo’s biochemical response was sustained through week 78 and may potentially reduce pruritus and improve itch-related quality of life in those with PBC.
“For a significant number of people living with PBC, available treatments do not control the condition and may exacerbate symptoms of PBC. Left unmanaged, PBC can progress, leading to liver failure and, in some cases, the need for a liver transplant,” Christelle Huguet, executive vice president and head of research and development at Ipsen, said. “Iqirvo demonstrated statistically significant improvements in biochemical response compared to UDCA alone. Iqirvo is therefore a much-needed treatment option and the first new medicine for PBC in nearly a decade.”
Data from the ELATIVE trial has yet to show improvement in survival or prevention of liver decompensation events. Therefore, continued approval “may be contingent upon verification and description of clinical benefit in confirmatory trial(s),” the release stated.
Common adverse reactions were reported in at least 10% of patients, including weight gain, abdominal pain, diarrhea, nausea and vomiting. In addition, some patients experienced myalgia, myopathy and rhabdomyolysis, fractures, adverse effects on fetal and newborn development, drug-induced liver injury, hypersensitivity reactions or biliary obstruction.
Of note, Iqirvo is not recommended for patients who have or develop decompensated cirrhosis, the release said.
The company noted it has submitted requests seeking authorization of Iqirvo for PBC to the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency, with final regulatory decisions expected in the second half of 2024.
Perspective
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Dian-Jung Chiang, MD, MPH
The FDA approval of elafibranor as a second-line agent is much-welcomed news for many patients suffering from PBC, as well as for physicians treating this chronic illness.
It is estimated that up to 40% of patients with PBC do not achieve adequate response with first-line ursodeoxycholic acid and only up to 47% of those non-responders respond to the currently available second-line agent, obeticholic acid. Therefore, many patients with PBC suffer without available alternative treatment options.
Data from the pivotal ELATIVE study showed elafibranor will not only induce biochemical response in 51% of the ursodeoxycholic non-responders but also will achieve biochemical remission in 15% of those patients. Further, elafibranor is well-tolerated based on available data from the trial.
Despite promising results from the ELATIVE trial and the FDA approval of elafibranor as a second-line agent for PBC, it is worth noting that we do not yet have data on whether elafibranor could improve liver fibrosis stage, prevent cirrhosis or reduce mortality. Longer-term follow-up studies will be necessary to help us answer this question.
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