FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC

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The accelerated approval is based on data from the phase 3 ELATIVE trial demonstrating a reduction in alkaline phosphatase with elafibranor.

US FDA logo in black over a white background. | Credit: US Food and Drug Administration

Credit: US Food and Drug Administration

The US Food and Drug Administration has granted accelerated approval to elafibranor (Iqirvo) 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.1

Announced on June 10, 2024, the decision is based on reduction of alkaline phosphatase (ALP) in the multi-center, randomized, double-blind, placebo-controlled phase 3 ELATIVE trial evaluating the efficacy and safety of elafibranor 80 mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to ursodeoxycholic acid. Full results were presented at the American Association for the Study of Liver Disease (AASLD) meeting in 2023 and showed statistically significant improvements in biomarkers of disease progression across key endpoints with a significant treatment benefit achieved in the primary composite endpoint for biochemical response.1,2

According to a release from Ipsen, improvement in survival or prevention of liver decompensation events have not been demonstrated, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).1

“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, director at Liver Institute Northwest, Washington and a primary investigator on the ELATIVE study.1 “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.”

The ELATIVE trial demonstrated that 13 times more patients achieved the composite primary endpoint of biochemical response when treated with elafibranor plus UDCA (n = 108) versus placebo plus UDCA (n = 53) (51% versus 4% for a 47% treatment difference, respectively). Secondary endpoints showed normalization in ALP levels in only elafibranor-treated patients (15% for elafibranor plus UDCA versus 0% for placebo plus UDCA). Most patients (95%) received study treatment (elafibranor or placebo) in combination with UDCA.1

The decision comes less than a week after new efficacy and itch-related quality of life data from ELATIVE were presented during a late-breaking session at the European Association for the Study of the Liver (EASL) Congress in Milan, Italy, demonstrating the dual peroxisome-activated receptor (PPAR) alpha/delta agonist’s efficacy after 78 weeks of treatment and impact on the itch domain of the PBC-40 and 5-D Itch questionnaires in patients with moderate-to-severe pruritus.3

Prior to the FDA decision, elafibranor had not received approval from any regulatory authorities – it is still under review by the European Medicines Agency and the UK Medicines and Healthcare Products Regulatory Authority. It was granted Breakthrough Therapy Designation from the FDA in 2019 based on positive phase 2 data from a 12-week double-blind randomized placebo-controlled trial of patients with noncirrhotic PBC and inadequate response to ursodeoxycholic acid. The FDA accepted a New Drug Application from Ipsen and GENEFIT in late 2023 for elafibranor, assigning it a target Prescription Drug User Fee Act (PDUFA) date of June 10, 2024.4,5

“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 in a press release.1 “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.”

References:

  1. Ipsen. Ipsen’s Iqirvo® receives U.S. FDA accelerated approval as a first-in-class PPAR treatment for primary biliary cholangitis. June 10, 2024. Accessed June 10, 2024. https://www.ipsen.com/press-releases/ipsens-iqirvo-receives-u-s-fda-accelerated-approval-as-a-first-in-class-ppar-treatment-for-primary-biliary-cholangitis/
  2. Ipsen. Results from Ipsen’s ELATIVE® pivotal Phase III trial of elafibranor in PBC presented as late breaking data at AASLD congress and published in New England Journal of Medicine. Press releases. November 14, 2023. Accessed June 7, 2024. https://www.ipsen.com/us/press-releases/results-from-ipsens-elative-pivotal-phase-iii-trial-of-elafibranor-in-pbc-presented-as-late-breaking-data-at-aasld-congress-and-published-in-new-england-journal-of-medicine/
  3. Brooks, A. ELATIVE: Elafibranor Slows Disease Progression, Improves Itch-Related QoL in PBC. HCPLive. June 5, 2024. Accessed June 7, 2024. https://www.hcplive.com/view/elative-elafibranor-slows-disease-progression-improves-itch-related-qol-in-pbc
  4. Genefit. GENFIT announces FDA Grant of Breakthrough Therapy Designation to Elafibranor for the Treatment of PBC. Press Releases. April 18, 2019. Accessed June 7, 2024. https://ir.genfit.com/news-releases/news-release-details/genfit-announces-fda-grant-breakthrough-therapy-designation
  5. Ipsen. Ipsen confirms U.S. FDA grants priority review for New Drug Application for elafibranor for the treatment of rare cholestatic liver disease, PBC. Press releases. December 7, 2023. Accessed June 7, 2024. https://www.ipsen.com/press-releases/ipsen-confirms-u-s-fda-grants-priority-review-for-new-drug-application-for-elafibranor-for-the-treatment-of-rare-cholestatic-liver-disease-pbc/
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