US FDA Grants Accelerated Approval for Ipsen’s Iqirvo to Treat Primary Biliary Cholangitis

Overview

Ipsen announced that the US Food and Drug Administration (FDA) has granted accelerated approval for Iqirvo (elafibranor) 80 mg tablets for the treatment of primary biliary cholangitis (PBC) 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 US for eligible patients.

Accelerated Approval for This Indication

• This indication is approved under accelerated approval based on reduction of alkaline phosphatase (ALP). 
• Improvement in survival or prevention of liver decompensation events have not been demonstrated. 
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 
• Iqirvo is not recommended for people who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

Words from Executive Vice President: Ipsen

• “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, 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.”

About Iqirvo

• 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 III 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 (n=108) versus placebo plus UDCA (=53) (respectively 51% versus 4% for a 47% treatment difference). 
• 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 (n=108) versus 0% for placebo plus UDCA (n=53)). 
• Most patients (95%) received study treatment (Iqirvo or placebo) in combination with UDCA.

Adverse Reactions with Iqirvo

• The most common adverse reactions with Iqirvo reported in =10% of study participants were weight gain, abdominal pain, diarrhoea, 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.

From the Primary Investigator of Elative Study

• “Data from the pivotal phase III ELATIVE clinical trial demonstrated that Iqirvo is an effective second-line treatment for patients with PBC with favourable benefit and risk data,” said Dr. Kris Kowdley, director at Liver Institute Northwest, Washington and a primary investigator on the ELATIVE study. 
• “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.”

About PBC

• 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. 
• Impacting approximately 100,000 people in the US, the majority being women, 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 (pruritus).

Words from PBCers

• “People living with PBC can feel like the symptoms they experience are dismissed by family members, friends or even their doctors, because they have not experienced something similarly disruptive in their lives. People with PBC may also feel uncertainty around the disease progression and if, or when, their liver health may deteriorate,” said Carol Roberts, executive president of PBCers, a patient advocacy organization in the US providing support to people living with PBC. 
• “Earlier diagnosis and education about PBC, along with new treatment options are important to meet the current needs of people living with PBC.”

Iqirvo to the European Medicines Agency

• Iqirvo has been submitted to the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), seeking authorization for PBC, with final EMA and MHRA regulatory decisions anticipated in the second half of 2024. 
• The FDA approval of Iqirvo further strengthens Ipsen’s portfolio of treatments for rare cholestatic liver diseases available to patients in the US. 
• This includes our 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).

About Iqirvo

• Iqirvo (pronounced EYE-KER-VO) is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR) agonist indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. 
• While the mechanism is not well understood, pharmacological activity that is potentially relevant to Iqirvo therapeutic effects includes inhibition of bile acid synthesis through activation of PPAR-alpha and PPAR-delta. 
• In 2019, Iqirvo was granted Breakthrough Therapy Designation by the U.S Food and Drug Administration (FDA) in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA) the existing first-line therapy for PBC. 
• Iqirvo has not received approval by regulatory authorities outside of the US. Iqirvo is currently under regulatory review with the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). 
• Iqirvo was discovered and developed by GENFIT and Ipsen licensed the exclusive worldwide rights (except China, Hong Kong, Taiwan and Macau) to elafibranor from GENFIT in 2021.

FDA Accelerated Approval Program for Iqirvo

• Iqirvo has been granted approval under the FDA accelerated approval program, which allows for approval of medicines that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. 
• Under the programme, Ipsen is required to conduct a trial to confirm anticipated clinical benefit. The confirmatory trial for Iqirvo, ELFIDENCE, is ongoing.

Iqirvo is an 80 mg tablet administered orally once daily.

ELATIVE

• ELATIVE is a multi-center, randomized double-blind, placebo-controlled phase III clinical trial (n=161) that evaluated the efficacy and safety of Iqirvo 80mg once daily plus UDCA (n=108) versus placebo plus UDCA (n=53). 
• Iqirvo or placebo was administered in combination with UDCA in 95% of patients and as monotherapy in 5% of patients who were unable to tolerate UDCA.  
• The 52-week study was completed by 92% of participants with 97% of those who completed the study continuing in an extension study. 
• The results were published in the New England Journal of Medicine.

ELATIVE Outcomes

• The ELATIVE trial demonstrated that Iqirvo had a statistically significant treatment benefit with 51% of patients on Iqirvo achieving a biochemical response compared with 4% on the placebo arm, a treatment benefit of 47% (95% CI 32, 57; p<0.0001). 
• Biochemical response was defined as ALP less than 1.67 Upper Limit of Normal (ULN), an ALP decrease of greater than or equal to 15% from baseline and total bilirubin (TB) = ULN at week 52.
• ALP normalization at week 52 was a key secondary endpoint with 15% of Iqirvo-treated patients demonstrating normalization versus 0% placebo (p=0.002).

The significant biochemical response to Iqirvo was further supported by data demonstrating reductions from baseline in ALP levels were sustained through week 52 and response was rapid, seen as early as Week 4 in the Iqirvo group.

Adverse Reactions

The most common adverse reactions with Iqirvo reported in =10% of study participants were weight gain, abdominal pain, diarrhea, nausea and vomiting.

Ipsen

Ipsen is a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: oncology, rare disease and neuroscience.

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