FDA Grants Accelerated Approval to Iqirvo (elafibranor) for the Treatment of Primary Biliary Cholangitis

Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the U.S. 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 U.S. for eligible patients.

This indication is approved under accelerated approval based on the reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events has 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).

“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.”

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 Medicine1. 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.

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.

“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 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.”

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 U.S.2, 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).

“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 U.S. 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 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 U.S. 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).

REF : https://en.wikipedia.org/wiki/Elafibranor

FDA Grants Accelerated Approval to Iqirvo (elafibranor) for the Treatment of Primary Biliary Cholangitis

FDA Grants Priority Review for Daiichi Sankyo’s New Drug Application for CSF1R Inhibitor Pexidartinib for Treatment of Patients with TGCT, a Rare, Debilitating Tumor

  

Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) and granted Priority Review for pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT), which is associated with severe morbidity or functional limitations, and which is not amenable to improvement with surgery.  TGCT, also referred to as pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), is a non-malignant tumor of the joint or tendon sheath, which can be locally aggressive and debilitating in some patients. There are no currently approved systemic therapies for TGCT.

A Priority Review designation is granted by the FDA to drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. Under Priority Review, the FDA aims to take action on an application within six months, as compared to ten months under standard review. The FDA has designated August 3, 2019 as the PDUFA Action date for this application. 

On January 31, 2019, the American Society of Clinical Oncology (ASCO) recognized “Progress in Treating Rare Cancers” as the “Advance of the Year”, and selected pexidartinib as one of five significant advancements in rare disease treatment, calling it the first promising investigational therapy for TGCT.

The NDA is based on results of the pivotal phase 3 ENLIVEN study of oral pexidartinib, the first placebo-controlled study of a systemic investigational therapy in patients with TGCT. Results of the phase 3 ENLIVEN study were presented during an oral presentation at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

“We are pleased to announce that the FDA has accepted our application for pexidartinib with Priority Review designation, potentially bringing a treatment option to patients for whom there is no approved therapy,” said Dale Shuster, Ph.D., Executive Director, Global Oncology R&D, Daiichi Sankyo. “Current treatment options for TGCT are largely limited to surgery, but for some patients the disease is debilitating and not amenable to improvement with surgery. We are committed to working with the FDA to potentially bring pexidartinib to carefully-selected patients as soon as possible.”

“We are excited about the first-in-class potential of pexidartinib, another targeted therapy discovered by Plexxikon,” said Gideon Bollag, Ph.D., Chief Executive Officer of Plexxikon Inc., Daiichi Sankyo’s small molecule structure-guided R&D center in Berkeley, CA and a member of the Daiichi Sankyo Group. “Our drug discovery process uses structural data and a specialized scaffold-like screening library to identify and optimize novel drug candidates.”

ENLIVEN is a pivotal, double-blind, randomized, global multi-center phase 3 study that evaluated pexidartinib in patients with symptomatic advanced TGCT for whom surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. The first part of the study, the double-blind phase, enrolled 120 patients who were randomized (1:1) to receive either pexidartinib or placebo at 1000 mg/d for 2 weeks followed by 800 mg/d for 22 weeks in order to evaluate the efficacy and safety of pexidartinib versus placebo. The primary endpoint of the study was the percentage of patients achieving a complete or partial response after 24 weeks of treatment (Week 25), as assessed with centrally-read MRI scans using RECIST 1.1 criteria. Key secondary endpoints included range of motion, response by tumor volume score, PROMIS physical function, stiffness and measures of pain reduction.

The ENLIVEN study met its primary endpoint of overall response rate. In the ENLIVEN study, hepatic toxicities were more frequent with pexidartinib versus placebo (AST or ALT ≥3X ULN: 33 percent, total bilirubin ≥2X ULN: 5 percent, N=61). Eight patients discontinued pexidartinib due to hepatic adverse events (AEs); four were serious nonfatal AEs with increased bilirubin, one lasting ~7 months. In non-TGCT development studies using pexidartinib, two severe liver toxicity cases (one required liver transplant, one was associated with death) were observed.

https://en.wikipedia.org/wiki/Pexidartinib