PARIS, France – Ipsen announced today 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.
“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 Christelle Huguet, EVP and Head of Research and Development, Ipsen. “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 U.S.”
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.
“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 Dr. Zev Wainberg, Professor of Medicine and Co-Director of the UCLA GI Oncology Program. “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.”
“We are pleased that the U.S. 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,” said Julie Fleshman, JD, MBA, President and CEO of Pancreatic Cancer Action Network (PanCAN), a patient advocacy organization committed to providing evidence-based information and resources to patients and caregivers, along with advancing research to improve patient outcomes. “We are thankful to the patients who participated in this clinical trial as they play a crucial role in advancing treatments for pancreatic cancer.”
NAPOLI 3 data
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.1,7Additionally, 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.
*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
About Onivyde (irinotecan liposome injection)
Onivyde is a cancer medicine that blocks an enzyme called topoisomerase I, which is involved in copying cell DNA needed to make new cells. By blocking the enzyme, cancer cells are prevented from multiplying and eventually die. In Onivyde, irinotecan is enclosed in tiny fat particles called ‘liposomes’, which accumulate in the tumor and release slowly over time. Onivyde is administered via intravenous infusion over 90 minutes every two weeks, with recommendations on dosing modifications. Onivyde may be prescribed immediately in the U.S. for eligible people living with mPDAC who are treatment naïve or following gemcitabine-based therapy.
To support access to Onivyde for eligible individuals in the U.S., Ipsen Cares patient support program is available as a resource to people living with mPDAC and their caregivers to provide educational support and address coverage, access and reimbursement questions (1-866-435-5677).
Onivyde is currently approved in most major markets including the U.S., Europe and Asia in combination with fluorouracil (FU) and leucovorin (LV) for the treatment of adult patients with metastatic pancreatic adenocarcinoma after disease progression following gemcitabine-based therapy. Onivyde is not indicated as a single agent for the treatment of adult patients with metastatic pancreatic adenocarcinoma.
In 2020, the FDA granted Ipsen Fast Track designation for Onivyde as a first-line combination treatment for mPDAC. The FDA’s Fast Track program facilitates the development and expedites the review of medicines that treat serious conditions and have the potential to address an unmet medical need.
Ipsen has exclusive commercialization rights for the current and potential future indications for Onivyde in the U.S. Servier, an independent international pharmaceutical company with an international presence in 150 countries, is responsible for the commercialization of Onivyde outside of the U.S. and Taiwan. PharmaEngine is a commercial stage oncology company headquartered in Taipei and is responsible for the commercialization of Onivyde in Taiwan.
About PDAC
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). Weight loss, abdominal pain and jaundice are the most common symptoms, making PDAC difficult to detect. Despite significant advances in cancer treatments since the 1970s, no treatment options for PDAC significantly extend life. Currently, fewer than 20% of people diagnosed with PDAC survive longer than one year and, overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S.
About the NAPOLI 3 trial
NAPOLI 3 is a randomized, open-label Phase III trial of an investigational Onivyde treatment regimen (NALIRIFOX) in patients who have not previously received chemotherapy for mPDAC. NAPOLI 3 enrolled 770 patients across 187 trial site locations in 18 countries across Europe, North America, South America, Asia, and Australia. Patients were randomized to receive Onivyde plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX regimen; n=383) twice in a month (days 1 and 15 of 28-day cycle) compared to an injection of nab-paclitaxel and gemcitabine (n=387) administered three times a month (days 1, 8, 15 of a 28-day cycle).
About Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience.
Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries.
Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY).
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