Palovarotene

Ipsen’s Onivyde regimen is indicated as a first-line treatment for metastatic pancreatic adenocarcinoma. Credit: MattL_Images / Shutterstock.com. The US Food and Drug Administration approved Ipsen ‘s supplemental new drug application for the Onivyde (irinotecan liposome injection) combination regimen (NALIRIFOX) as a first-line treatment for metastatic pancreatic adenocarcinoma (mPDAC) in adults. The treatment is indicated for use with oxaliplatin, fluorouracil and leucovorin. It is the second FDA approval for an Onivyde regimen in mPDAC, expanding treatment options for patients. In 2015, the regulator approved Onivyde plus fluorouracil and leucovorin in patients experiencing disease progression following gemcitabine-based therapy. The latest approval is based on findings from the Phase III NAPOLI 3 clinical trial. See Also: FDA grants fast track status to Edgewise’s Duchenne treatment SCOPE: FDA facilitates AI and ML use for clinical trials and drug development The open-label, randomised trial enrolled 770 individuals across 187 sites in 18 countries. The trial met its primary and secondary endpoints, showing improvements in survival rates for subjects treated with the Onivyde regimen compared to those receiving nab-paclitaxel and gemcitabine. Patients treated with the Onivyde regimen, NALIRIFOX, experienced a median overall survival of 11.1 months, notably longer than the 9.2 months observed in patients treated with nab-paclitaxel and gemcitabine. The Onivyde combination also led to a median progression-free survival of 7.4 months, compared to 5.6 months under the alternative treatment. The objective response rate for the NALIRIFOX regimen was 41.8%, against the 36.2% rate for those receiving nab-paclitaxel and gemcitabine. Despite the potential for serious adverse events such as fatal neutropenic fever and severe diarrhoea, the safety profile of the Onivyde regimen was deemed manageable. Ipsen Research and Development EVP and head Christelle Huguet stated: “With today’s approval, this Onivyde (NALIRIFOX) regimen can now offer a potential new standard-of-care treatment option with proven survival benefits for people living with metastatic pancreatic adenocarcinoma in the US.” Ipsen holds sole rights to market Onivyde in the US for existing and future indications while Servier will commercialise the therapy outside the US and Taiwan. In August 2023, Ipsen received FDA approval for Sohonos (palovarotene) capsules to treat fibrodysplasia ossificans progressiva .

Pictured: FDA's signage at its campus in Maryland/iStock, JHVEPhoto The FDA on Tuesday approved Ipsen’s Onivyde (irinotecan liposome injection), when used in combination with three chemotherapeutic drugs, for the treatment of newly diagnosed patients with metastatic pancreatic adenocarcinoma. The Onivyde-based regimen, dubbed Nalirifox, is the first frontline approval for metastatic pancreatic adenocarcinoma (mPDAC) in more than 10 years, Julie Fleshman, CEO of patient advocacy group Pancreatic Cancer Action Network, said in a statement. Christelle Huguet, Ipsen’s executive vice president and head of R&D, said in a statement that Onivyde’s latest approval “can now offer a potential new standard-of-care treatment option with proven survival benefits” for mPDAC patients. Tuesday’s label expansion is based on data from the Phase III NAPOLI 3 trial, a randomized, open-label pivotal study with 770 mPDAC patients enrolled, all of whom had undergone no prior treatment. In January 2023, Ipsen posted data from NAPOLI 3, demonstrating that the Nalirifox regimen—which combines Onivyde with fluorouracil, oxaliplatin and leucovorin—boosted overall survival by a statistically significant 17% compared to standard of care, consisting of nab-paclitaxel and gemcitabine. Nalirifox also improved progression-free survival by 31%. According to Ipsen’s announcement, NAPOLI 3 is the first positive Phase III trial in mPDAC that shows better overall survival compared to the current standard-of-care regimen, and Onivyde is the only FDA-approved treatment regimen to demonstrate efficacy in two Phase III trials across lines of therapy in mPDAC. Onivyde encloses the chemotherapeutic drug irinotecan in liposomes, which can accumulate inside tumors over time, slowly releasing a toxic payload. By blocking the topoisomerase I enzyme, which is involved in DNA replication and is crucial for cell proliferation, Onivyde exerts its cancer-killing effects. The FDA first approved Onivyde, in combination with fluorouracil and leucovorin, in 2015 for mPDAC patients who had progressed after gemcitabine-based treatment. Tuesday’s label expansion continues a winning streak for Ipsen. In June 2023, the biotech secured the support of the Metabolic Drugs Advisory Committee, voting 10–4 to recommend the approval of its fibrodysplasia ossificans progressiva therapy palovarotene. In August 2023, the FDA followed the advice of its external experts and approved the therapy, which now carries the brand name Sohonos. Ipsen has also been on a clinical roll. In June 2023, the company revealed topline data from its Phase III ELATIVE trial for elafibranor, demonstrating a significantly higher rate of clinically meaningful cholestasis versus placebo in patients with primary biliary cholangitis. Ipsen, along with partner Genfit, followed this up with strong biochemical response data in November 2023. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.