Merrimack announced that Onivyde (irinotecan liposome injection) has been approved by the US Food and Drug Administration (FDA) in combination with fluorouracil (5-FU) and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. Onivyde is not indicated for use as a single agent.

With this approval, Onivyde in combination with 5-FU and leucovorin becomes the first and only FDA-approved treatment option for patients in this setting.

"This is an important day for patients facing pancreatic cancer," said Andrea Wang-Gillam, M.D., Ph.D., associate professor of medicine, clinical director of GI Oncology Programme, Division of Oncology, at Washington University School of Medicine, St. Louis, and a key investigator on the Onivyde phase 3 NAPOLI-1 study.

"With a long history of failed clinical studies in the post-gemcitabine setting, this approval is a significant achievement in the oncology community. It brings a new therapy to the many patients who are facing this aggressive disease and are in need of treatment options."

"We are thrilled to be able to deliver this groundbreaking therapy to patients battling metastatic pancreatic cancer," said Robert Mulroy, president and CEO of Merrimack.

"Pancreatic cancer is an aggressive and devastating disease, with very few patients surviving beyond one year. Onivyde provides a clinically significant treatment option to a patient population where there is currently no standard of care. We are grateful to the many patients, clinicians, researchers and partners that worked with us to make Onivyde available. Today's approval by the FDA is a pivotal milestone in our company's history, representing years of hard work and commitment to our mission of engineering new treatment options for cancer patients in need."

The FDA approval is based on the results of an international phase 3 randomized, controlled study (NAPOLI-1). In this study, Onivyde in combination with 5-FU and leucovorin achieved its primary endpoint of a significant improvement in overall survival (p=0.014, unstratified HR=0.68, 95 per cent CI: [0.50-0.93]) with a 45 per cent improvement in median overall survival of 6.1 months for patients receiving the Onivyde combination regimen compared to 4.2 months for patients who received 5-FU and leucovorin alone. The Onivyde combination also demonstrated improvement in progression free survival (3.1 months vs. 1.5 months, HR=0.55, 95 per cent CI: [0.41-0.75]). The monotherapy regimen in this study did not achieve its primary endpoint and, therefore, Onivyde is not indicated as a single agent. The most common adverse reactions ( > 20 per cent) of Onivyde were diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, stomatitis and pyrexia, and the most common severe laboratory abnormalities ( > 10 per cent Grade 3 or 4) were lymphopenia and neutropenia.

"This is a pivotal achievement for the pancreatic cancer community because it provides a new treatment option for some patients facing this difficult disease," said Julie Fleshman, president and CEO of the Pancreatic Cancer Action Network. "We applaud the dedication of those involved in this advancement, knowing it will impact our goal to double pancreatic cancer survival by 2020."

There are approximately 49,000 patients diagnosed with pancreatic cancer each year in the United States, the overwhelming majority of whom have adenocarcinoma. Most patients receive gemcitabine-based therapy during either adjuvant/neoadjuvant treatment for locally advanced disease or during first- or second-line therapy for metastatic disease, but are left with no standard of care therapy upon progression. Onivyde in combination with 5-FU and leucovorin is now approved for these patients whose disease has progressed following gemcitabine-based therapy.

Merrimack expects Onivyde to be available in the United States next week and is committed to supporting rapid physician and patient access to this therapy. Provyde (Onivyde Access Center) offers a variety of reimbursement support services for healthcare providers and financial assistance services for patients.

Baxalta Incorporated is responsible for the development and commercialisation of Onivyde outside of the United States and Taiwan under the exclusive licensing agreement that Merrimack and Baxalta entered into in September 2014. In May 2015, the European Medicines Agency (EMA) accepted for review Baxalta's marketing authorisation application (MAA) for Onivyde based on the same clinical results.

"We are excited that Onivyde (nal-IRI) will now be available to people living with metastatic pancreatic cancer in the US after they progress from gemcitabine-based therapy," said David Meek, executive vice president and president of oncology at Baxalta.

"Looking ahead, Baxalta continues to work toward marketing authorisation in Europe with the goal of providing nal-IRI to patients in more countries around the world in need of new options."

PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialise Onivyde in Taiwan. PharmaEngine filed a New Drug Application (NDA) with the Taiwan FDA in May 2015.

The NAPOLI-1 study was a randomized, open label phase 3 study in patients with metastatic adenocarcinoma of the pancreas who received prior gemcitabine-based therapy, and was the largest Phase 3 study in this setting to date. The study evaluated Onivyde in combination with 5-FU and leucovorin administered every two weeks and as a monotherapy administered every three weeks. Each Onivyde containing arm was compared to a control arm of 5-FU and leucovorin. A total of 417 patients were randomized across the three arms. The primary endpoint of the study was overall survival. The Onivyde combination regimen demonstrated a significant increase in median overall survival versus 5-FU and leucovorin alone: 6.1 months vs 4.2 months (p=0.014, unstratified HR=0.68, 95 per cent CI: [0.50-0.93]). The monotherapy regimen in this study did not show improvement over the 5-FU and leucovorin arm (HR=1.00, p=0.97 [unstratified log-rank test]). Patients were enrolled at 76 sites in North America, South America, Europe, Asia and Oceania.

Pancreatic cancer is rare and deadly. It accounts for only 3 per cent of all cancer cases, but is the fourth leading cause of cancer-related death4, leading to a five year survival rate of only 7 per cent. Each year an estimated 49,000 new cases are diagnosed in the United States, two-thirds of which are among people aged 65 or older. There are an estimated 338,000 new cases diagnosed each year worldwide.

The pancreas is composed of two main cell types: exocrine and endocrine. Exocrine tumors are the most common type of pancreatic cancer, accounting for 96 per cent of all cases. Adenocarcinoma, a sub-type of exocrine tumours, comprises 95 per cent of all exocrine tumours.

Because the signs and symptoms of pancreatic cancer are non-specific and may not appear until the disease has spread to other sites, approximately 80 per cent of patients are not candidates for surgery4, instead receiving chemotherapy as the mainstay of their therapy. The majority of these patients receive gemcitabine-based therapy during either adjuvant/neoadjuvant treatment or during first- or second-line therapy for metastatic disease. There is no consensus on the standard of care for patients with metastatic pancreatic cancer previously treated with a gemcitabine-based therapy.

Onivyde, also known as MM-398 or "nal-IRI," is a novel encapsulation of irinotecan in a liposomal formulation. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death.