Promising NAPOLI 3 Trial Results Lead to FDA Approval of Onivyde Regimen for Metastatic Pancreatic Adenocarcinoma

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The FDA has approved Ipsen’s Onivyde (irinotecan liposome injection) in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) for the first-line treatment of patients with metastatic pancreatic adenocarcinoma (mPDAC). The FDA initially approved an Onivyde treatment combination for mPDAC in 2015 in combination with fluorouracil and leucovorin for patients who experienced disease progression with gemcitabine-based therapy.

“The results from the Phase III NAPOLI 3 trial represent the first positive data for an investigational regimen in first-line metastatic pancreatic adenocarcinoma versus the currently approved nab-paclitaxel and gemcitabine regimen,” said Ipsen EVP and Head of Research and Development Christelle Huguet, in a press release. “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.”¹

Onivyde acts by blocking the topoisomerase I enzyme, which plays a role in copying the cell DNA required to produce new cells, which inhibits cancer cells from multiplying and leads to cell death.

Approximately 66,440 individuals will be diagnosed with pancreatic cancer in 2024, with approximately 51,750 deaths, according to the American Cancer Society. The disease comprises approximately 3% of all cancer diagnoses in the United States and approximately 7% of total cancer deaths.²

PDAC is the most common form of the disease, with more than 60,000 diagnoses per year in the United States and approximately 500,000 people globally. Lacking specific symptoms in the early stages, PDAC is frequently not diagnosed until late stages after it has become metastatic or stage IV. Fewer than 20% of patients diagnosed with PDAC survive longer than a year.¹

The safety and efficacy of NALIRIFOX were evaluated in the open-label, multicenter, randomized Phase III NAPOLI 3 trial (NCT04083235). The combination was found to significantly improve overall survival compared with gemcitabine and nab-paclitaxel (Abraxane; n = 387), showing a median of 11.1 months with the combination compared with 9.2 months in the control group, which translates to a 16% drop in the risk of death.

NALIRIFOX were also found to improve progression-free survival compared with gemcitabine/nab-paclitaxel, at a median of 7.4 months compared with 5.6 months, respectively, which translates to a 30% drop in the risk of disease progression or death. The NALIRIFOX combination produced an objective response rate of 41.8% compared to 36.2% with gemcitabine/nab-paclitaxel.

“Metastatic pancreatic adenocarcinoma is a difficult disease to manage with very few available treatment options. Given the reality of this aggressive form of cancer and the complexity of the disease, every advance in the treatment landscape represents a meaningful improvement in patient outcomes.” said Zev Wainberg, MD, professor of Medicine and co-director of the UCLA GI Oncology Program, said in a press release. “The approval of this Onivyde regimen is an important milestone for people living with mPDAC, their families and healthcare providers, with the NAPOLI 3 trial having demonstrated survival benefits versus a current standard of care treatment option.”¹

In terms of safety, the most common adverse events reported with NALIRIFOX occurring in at least 20% of patients included diarrhea, fatigue, nausea, vomiting, reduced appetite, abdominal pain, mucosal inflammation, constipation, and reduced weight.

“We are pleased that the US Food and Drug Administration has issued this new approval of the NALIRIFOX regimen. With each new approved treatment, there is more hope for those who will be diagnosed in the future and people currently living with pancreatic cancer may have more time with their loved ones,” Julie Fleshman, JD, MBA, president and CEO of Pancreatic Cancer Action Network, said in the release. “We are thankful to the patients who participated in this clinical trial as they play a crucial role in advancing treatments for pancreatic cancer.”¹

References

1. Ipsen’s Onivyde® regimen, a potential new standard-of-care first-line therapy in metastatic pancreatic adenocarcinoma, approved by FDA. Ipsen. News release. February 13, 2024. Accessed February 14, 2024. https://www.ipsen.com/press-releases/ipsens-onivyde-regimen-a-potential-new-standard-of-care-first-line-therapy-in-metastatic-pancreatic-adenocarcinoma-approved-by-fda/

2. Key Statistics for Pancreatic Cancer. American Cancer Society. Webpage. Updated January 19, 2024. Accessed February 14, 2024. https://www.cancer.org/cancer/types/pancreatic-cancer/about/key-statistics.html