FDA to Review Onivyde Regimen for Metastatic Pancreatic Cancer


The NALIRIFOX regimen of Onivyde plus 5-fluorouracil/leucovorin and oxaliplatin has been shown to have survival and disease progression benefits for patients with pancreatic cancer in a clinical trial setting.

human body, zoom in on the pancreas

After study findings showed that patients in the NALIRIFOX group had a median overall survival of 11.1 months, while those in the nab-paclitaxel and gemcitabine group had a median overall survival of 9.2 months, the FDA agreed to review the regimen for metastatic pancreatic cancer treatment.

The Food and Drug Administration (FDA) accepted a supplemental new drug application for Onivyde (irinotecan liposome injection) plus 5-fluorouracil/leucovorin and oxaliplatin (NALIRIFOX regimen) as a potential first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma, according to a press release from biopharmaceutical company, Ipsen.

The review follows the results from the phase 3 NAPOLI trial, comparing overall survival (the time from treatment until death of any cause) and progression-free survival (the time during and after treatment a patient lives without the disease worsening) of patients treated with Onivyde, administered twice in a month, versus those treated with nab-paclitaxel plus gemcitabine three times in a month.

An open-label, randomized clinical trial, NAPOLI 3, according to its listing on clinicaltrials.gov, began in February 2020 and had the participation of 770 patients ages 18 and older with histological or cytologically confirmed adenocarcinoma of the pancreas that had not been previously treated in the metastatic setting.

Patients in the NALIRIFOX group had a median overall survival of 11.1 months, while those in the nab-paclitaxel and gemcitabine group had a median overall survival of 9.2 months, according to data from Ipsen originally presented at the January 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The overall survival rates at 12 months were 45.6% and 39.5% for the NALIRIFOX and nab-paclitaxel and gemcitabine groups, respectively, and 26.2% and 19.3% at 18 months, Ipsen reported.

“(Pancreatic ductal adenocarcinoma) is a devastating disease in need of additional treatment options. The FDA’s decision to accept the sNDA for this Onivyde-based regimen in treatment-naïve patients with metastatic disease represents an important milestone in the potential treatment of this complex form of cancer,” Howard Mayer, executive vice president and head of research and development at Ipsen, said in the news release. “We’re committed to developing therapies which have the potential to make a meaningful difference to the lives of people living with cancer and look forward to working with FDA as they review this application.”

Patients in the NALIRIFOX group had a median progression-free survival of 7.4 months, compared to 5.6 months for patients in the nab-paclitaxel and gemcitabine group, according to Ipsen’s news release. The objective response rate (measuring how much tumors shrink from treatment) for patients treated with NALIRIFOX was 41.8% and was 36.2% for those treated with nab-paclitaxel and gemcitabine, according to the news release.

Onivyde, Ipsen explained in the press release, works by blocking topoisomersase I, an enzyme involved in copying cell DNA that is necessary for making new cells. “By blocking the enzyme, cancer cells are prevented from multiplying and eventually die,” Ipsen explained. “In Onivyde, irinotecan is enclosed in tiny fat particles called liposomes, which accumulate in the tumor and release slowly over time.”

The FDA approved Onivyde in combination with 5-fluorouracil chemotherapy and leucovorin for the treatment of patients with metastatic pancreatic cancer following prior administration of a gemcitabine-based regimen in 2015.

In NAPOLI 3, the safety profile of NALIRIFOX “was consistent with the profiles of the treatment components,” Ipsen reported, noting that the most common grade three and four treatment-emergent side effects with more than 10% frequency among patients in the NALIRIFOX group compared with those in the nab-paclitaxel and gemcitabine group included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (low levels of potassium, 15.1% vs 4.0%), anemia (10.5% vs 17.4%) and neutropenia (low levels of white blood cells, 14.1% vs 24.5%).

The FDA, which granted Fast Track designation for Onivyde as a first-line combination treatment for patients with mPDAC in 2020, set a Prescription Drug User Fee Act goal date of Feb. 13, 2024 for its review of the supplemental new drug application, Onivyde announced in the press release.

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