Ipsen announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application for Onivyde® (irinotecan liposome injection) plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) as a first-line treatment in adults living with metastatic pancreatic adenocarcinoma (mPDAC). This is the second approval for an Onivyde regimen in mPDAC, following the FDA?s approval in 2015 of Onivyde plus fluorouracil and leucovorin following disease progression with gemcitabine-based therapy. Pancreatic adenocarcinoma (PDAC) is the most common type of cancer that forms in the pancreas, with more than 60,000 people diagnosed in the U.S. each year and nearly 500,000 people globally.

Since there are no specific symptoms in the early stages, PDAC is often detected late and after the disease has spread to other parts of the body (metastatic or stage IV). Characterized as a complex cancer due to rapid tumor progression, limited genetic targets and multiple resistance mechanisms, mPDAC has a poor prognosis with fewer than 20% of people surviving longer than one year. Overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S. The FDA approval was based on efficacy and safety data from NAPOLI 3, a randomized, open-label, Phase III pivotal trial that enrolled 770 people living with mPDAC between the ages of 20 and 85 without prior treatment across 187 trial site locations in 18 countries.

The study, which met the primary and secondary endpoints, was presented as a late-breaking presentation at the ASCO Gastrointestinal conference 2023 and subsequently published in The Lancet. Additionally, NALIRIFOX was recognized by the National Comprehensive Cancer Network® (NCCN) guidelines and recommended as a preferred, Category 1 treatment option in first-line metastatic disease and as a preferred option in first-line locally advanced disease. The study demonstrated NALIRIFOX (n=383) provided a statistically significant improvement in median overall survival (mOS) of 11.1 months (95% confidence interval (CI) (10.0, 12.1)) compared to 9.2 months (95% CI (8.3, 10.6)) in nab-paclitaxel and gemcitabine treated patients (n=387); (hazard ratio (HR) 0.84 [95% CI 0.71?0.99]; p=0.0403).

NALIRIFOX regimen also demonstrated a statistically significant improvement in median progression-free survival (mPFS) of 7.4 months (95% CI (6.0, 7.7)) versus 5.6 months (95% CI (5.3, 5.8)) for nab-paclitaxel and gemcitabine treated patients (HR 0.70 [95% CI 0.59?0.85]; p=0.0001). The objective response rate was 41.8% (36.8%-46.9%; 95% CI) for patients treated with the NALIRIFOX regimen versus 36.2% (31.4%-41.2%; 95% CI) for patients treated with nab-paclitaxel and gemcitabine. The safety profile of the Onivyde regimen was manageable and consistent with the profiles of the treatment components, with the potential of serious adverse events of fatal neutropenic fever and severe diarrhea.

The most common Grade 3/4 treatment-emergent adverse events were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation and decreased weight. In NAPOLI 3, Grade 3 and 4 diarrhea (early and late-onset) occurred in 20% receiving NALIRIFOX. In the clinical trial, diarrhea was managed following institutional guidelines and appropriate antidiarrheal medications.