Ipsen’s Iqirvo(R) receives U.S. FDA accelerated approval as a first-in-class PPAR treatment for primary biliary cholangitisimary biliary cholangitis

The U.S. FDA granted accelerated approval for Iqirvo as a first-in-class PPAR treatment for primary biliary cholangitis. Iqirvo is the first new medicine approved in nearly a decade for this rare liver disease.

Clinical Trial Data:

• The approval was based on positive Phase III ELATIVE trial data.

• The trial showed significant biochemical response improvements with Iqirvo compared to UDCA alone.

PBC Impact and Treatment Need:

• Primary biliary cholangitis affects approximately 100,000 people in the US and can lead to liver failure if inadequately treated.

• Iqirvo provides a much-needed treatment option for those with PBC, addressing symptoms and disease progression.

Iqirvo Features and Risks:

• Iqirvo is a first-in-class PPAR agonist, offering once-daily dosing.

• Common adverse reactions include weight gain, abdominal pain, and gastrointestinal issues.

Physician's Perspective:

• Dr. Kris Kowdley emphasized that Iqirvo is an effective second-line treatment for PBC.

• The approval of Iqirvo presents a significant benefit for patients with PBC in terms of ALP level reduction.

PBC Impact on Patients:

• PBC is a rare autoimmune liver disease that can lead to irreversible fibrosis and bile duct damage.

• People with PBC commonly experience severe fatigue and intense itching.

Patient Advocacy and Education:

• Patient advocacy organizations highlight the importance of early diagnosis and education about PBC.

• New treatment options like Iqirvo are vital to meet the current needs of individuals living with PBC.

Regulatory Outlook and Portfolio Expansion:

• Iqirvo is under review by the EMA and MHRA for PBC authorization.

• FDA approval strengthens Ipsen's portfolio for rare cholestatic liver diseases.

Hypersensitivity Reactions:

• Permanently discontinue IQIRVO for severe reactions. For mild or moderate reactions, interrupt treatment, monitor, and resume cautiously.

• If hypersensitivity recurs after rechallenge, discontinue IQIRVO indefinitely.

Biliary Obstruction:

• Avoid IQIRVO in complete biliary obstruction cases.

• If suspected, interrupt treatment and manage the patient clinically.

Drug-Drug Interactions:

• IQIRVO can impact the exposure of certain drugs (CYP3A4 substrates). Consider alternative contraceptives during treatment and post-treatment.

• Be cautious when combining IQIRVO with HMG-CoA reductase inhibitors to monitor for myopathy.

Co-administration Concerns:

• Combining IQIRVO with rifampin may impact its efficacy. Monitor biochemistry when initiating rifampin.

• Administer IQIRVO separately from bile acid sequestrants for optimal absorption.

Special Populations:

• Pregnant or breastfeeding women should avoid IQIRVO due to potential harm to the fetus or breastfed child.

• Females of reproductive potential must confirm pregnancy status and use effective contraception during and after treatment.

Adverse Events:

• Common adverse events include weight gain, abdominal pain, nausea, vomiting, and diarrhea.

• Report side effects to FDA or Ipsen Pharmaceuticals for monitoring.

About Iqirvo:

• Iqirvo is a PPAR agonist for treating PBC in combination with UDCA.

• It was granted Breakthrough Therapy Designation by the FDA and is under regulatory review in Europe.

Phase III ELATIVE Trial:

• ELATIVE trial showed significant efficacy of Iqirvo in achieving biochemical response in PBC patients.

• Common adverse reactions include weight gain, abdominal pain, diarrhea, nausea, and vomiting.

Iqirvo FDA Approval:

• The U.S. 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, establishing Ipsen as a leader in the treatment of rare cholestatic liver diseases.

Iqirvo Efficacy:

• Iqirvo demonstrated statistically significant improvements in biochemical response compared to UDCA alone, as evidenced in the Phase III ELATIVE trial.

• The ELATIVE trial showed that a significantly higher percentage of patients achieved the composite primary endpoint of biochemical response when treated with Iqirvo plus UDCA compared to placebo plus UDCA.

Iqirvo Safety and Side Effects:

• Common adverse reactions with Iqirvo reported in ≥10% of study participants include weight gain, abdominal pain, diarrhea, nausea, and vomiting.

• Some study participants treated with Iqirvo experienced adverse effects such as myalgia, myopathy, rhabdomyolysis, fractures, drug-induced liver injury, hypersensitivity reactions, or biliary obstruction.

Impacts of PBC:

• PBC is a rare, autoimmune, cholestatic liver disease affecting approximately 100,000 people in the U.S., with the majority being women.

• The disease can lead to irreversible fibrosis of the liver and destruction of the bile ducts, impacting day-to-day life with severe fatigue symptoms and debilitating itch.

Unmet Need Addressed:

• The approval of Iqirvo will allow healthcare providers in the U.S. to address an unmet need and potentially significantly reduce alkaline phosphatase (ALP) levels for patients with PBC.

• Iqirvo is seen as a much-needed treatment option and the first new medicine for PBC in nearly a decade.

Future Expectations:

• Ipsen’s expectations regarding future events, regulatory filings, and determinations indicate a positive outlook for the potential impact of Iqirvo in the treatment of PBC.

• The targets described in the document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters.

Risks and Uncertainties:

• Ipsen faces or might face competition from generic medicine, potential failure of medicine development stages, and challenges in obtaining regulatory approvals.

• Other risks include general industry conditions, economic factors, technological advances, and dependence on third parties for drug development and marketing.

Disclosures and Disclaimers:

• Ipsen expressly disclaims any obligation to update or revise forward-looking statements, targets, or estimates to reflect any change in events, conditions, assumptions, or circumstances.

• The risks and uncertainties outlined are not exhaustive, and readers are advised to refer to Ipsen’s latest Universal Registration Document.

Iqirvo Overview:

• Iqirvo is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR) agonist indicated for the treatment of primary biliary cholangitis (PBC).

• It can be used in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.

Regulatory Progress:

• Iqirvo has been submitted for authorization to the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

• Final regulatory decisions from EMA and MHRA are expected in the second half of 2024.

FDA Approval:

• Iqirvo has received FDA approval for the treatment of primary biliary cholangitis (PBC) in the U.S.

• It adds to Ipsen's portfolio of treatments for rare cholestatic liver diseases.

Important Safety Information:

• Risks associated with Iqirvo include myalgia, myopathy, rhabdomyolysis, fractures, adverse effects on fetal development, drug-induced liver injury, hypersensitivity reactions, and biliary obstruction.

• Special precautions are needed for drug-drug interactions and use in special populations like pregnant and lactating women.

Adverse Events:

• Common adverse events with Iqirvo include weight gain, abdominal pain, nausea, vomiting, and diarrhea.

• These should be monitored and reported to the FDA and Ipsen Pharmaceuticals.

Drug Administration:

• Iqirvo is an 80 mg tablet taken orally once daily.

• Patients should be informed about the correct administration and potential side effects of the medication.

Breakthrough Therapy Designation:

• In 2019, Iqirvo was granted Breakthrough Therapy Designation by the U.S. FDA for adults with PBC.

• This designation highlights the need for improved treatment options in this patient population.

IPSEN CARES® Program:

• To ensure access to Iqirvo in the U.S., the IPSEN CARES® patient support program provides educational support and addresses coverage, access, and reimbursement questions.

• This program serves as a valuable resource for individuals living with PBC and their caregivers.

Phase III ELATIVE Trial Overview:

• The Phase III ELATIVE trial evaluated Iqirvo 80mg plus UDCA versus placebo plus UDCA in 161 participants.

• 52-week study completion rate was 92%, with 97% continuing into an extension study.

Treatment Benefits of Iqirvo:

• Iqirvo showed a significant treatment benefit with 51% achieving a biochemical response compared to 4% on placebo.

• ALP normalization at week 52 was seen in 15% of Iqirvo-treated patients.

Sustained Biochemical Response:

• Data showed sustained reductions in ALP levels through week 52 with rapid response seen as early as Week 4.

• ALP normalization at Week 52 was significantly higher in the Iqirvo group.

Adverse Reactions with Iqirvo:

• Common adverse reactions with Iqirvo included weight gain, abdominal pain, diarrhea, nausea, and vomiting.

• These reactions were reported in ≥10% of study participants.

About Ipsen:

• Ipsen is a global biopharmaceutical company focusing on Oncology, Rare Disease, and Neuroscience.

• Their pipeline is driven by external innovation and decades of development experience.

IVYDE® REGIMEN, A POTENTIAL NEW STANDARD-OF-CARE FIRST-LINE THERAPY IN METASTATIC PANCREATIC ADENOCARCINOMA:

• Ivyde® regimen has been approved by the FDA as a potential new standard-of-care first-line therapy in metastatic pancreatic adenocarcinoma.

• The approval marks a significant advancement in the treatment options for this type of cancer.