FDA Grants Accelerated Approval to Ipsen Iqirvo for Rare Liver Disease

Rare Daily Staff

The U.S. Food and Drug Administration granted Ipsen accelerated approval for Iqirvo, its treatment for the rare liver disease primary biliary cholangitis.

The approval is for Iqirvo in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Iqirvo may be prescribed immediately in the United States for eligible patients.

The approval of Iqirvo further strengthens Ipsen’s portfolio of treatments for rare cholestatic liver diseases available to patients in the United States. This includes its FDA approved medicine for the treatment of pruritus in patients three months and older with progressive familial intrahepatic cholestasis (PFIC) and for the treatment of cholestatic pruritus in patients from 12 months of age with Alagille syndrome (ALGS).

Primary biliary cholangitis (PBC) is a rare, autoimmune, cholestatic liver disease where a build-up of bile and toxins (cholestasis) and chronic inflammation causes irreversible fibrosis (scarring) of the liver and destruction of the bile ducts. PBC is a lifelong condition that can worsen over time if not effectively treated, leading to liver transplant and in some cases, premature death. PBC also affects day-to-day life, with people most commonly experiencing severe fatigue symptoms and debilitating itch.

Iqirvo is a first-in-class oral, once-daily peroxisome proliferator-activated receptor (PPAR) agonist. Iqirvo was in-licensed from Genfit in 2021. The accelerated approval of Iqirvo is based on data from the phase 3 ELATIVE trial published in the New England Journal of Medicine.

The ELATIVE trial demonstrated that 13 times more patients achieved the composite primary endpoint of biochemical response when treated with Iqirvo plus UDCA (51 percent) versus placebo plus UDCA (4 percent).

The FDA approved the indication under accelerated approval based on reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. ALP is a biochemical marker and is used as a surrogate endpoint in PBC trials. Secondary endpoints showed normalization in ALP levels in only Iqirvo-treated patients (15% for Iqirvo plus UDCA versus 0 percent for placebo plus UDCA). Most patients (95 percent) received study treatment (Iqirvo or placebo) in combination with UDCA.

The most common adverse reactions with Iqirvo reported in ≥10% of study participants were weight gain, abdominal pain, diarrhea, nausea, and vomiting. Some study participants treated with Iqirvo experienced myalgia, myopathy, and rhabdomyolysis; fractures; adverse effects on fetal and newborn development; drug-induced liver injury; hypersensitivity reactions; or biliary obstruction. See full Important Safety Information below.

Continued approval for the indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Iqirvo is not recommended for people who have or develop decompensated cirrhosis.

Iqirvo has been submitted to the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency, seeking authorization for PBC, with final EMA and MHRA regulatory decisions anticipated in the second half of 2024.

“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,” said Christelle Huguet, executive vice president and head of research and development at Ipsen. “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.”

Photo: Christelle Huguet, executive vice president and head of research and development at Ipsen