Merrimack Pharmaceuticals, Inc., a biopharmaceutical company, and Baxalta Incorporated, a wholly-owned subsidiary of Baxter International Inc, jointly announced that the New Drug Application (NDA) for MM-398 (irinotecan liposome injection), also known as "nal-IRI," has been accepted for review by the US Food and Drug Administration (FDA).
Merrimack is seeking US marketing approval of MM-398 for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy.
In addition, the FDA has classified the NDA as having Priority Review status. A Priority Review designation is for drugs that treat serious conditions and, if approved, would provide significant improvements in the safety or effectiveness of the treatment of serious conditions compared to available therapies. The FDA has set a goal of October 24, 2015 to take action under the Prescription Drug User Fee Act (PDUFA).
"The rapid timeline associated with Priority Review designation brings Merrimack closer to our goal of making MM-398 available to patients with pancreatic cancer who have been previously treated with gemcitabine and are in significant need of treatment options," said Robert Mulroy, president and chief executive officer, Merrimack. "We look forward to working with the FDA as they review the application over the next several months."
Merrimack's application is based upon the results of an international phase 3 study (NAPOLI-1) conducted in patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. MM-398 in combination with 5-fluorouracil (5-FU) and leucovorin achieved its primary and secondary endpoints by demonstrating a statistically significant improvement in overall survival, progression free survival and overall response rate compared to the control group of patients who received a combination of 5-FU and leucovorin. The most common Grade 3 or higher adverse events in patients receiving MM-398 and 5-FU/LV were neutropenia, fatigue and gastrointestinal effects. This was the first global phase 3 study in a post-gemcitabine setting to show a survival benefit in this aggressive disease. Data for the study were presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer (ESMO GI) in June 2014 and the American Society of Clinical Oncology 2015 Gastrointestinal Cancers Symposium (ASCO GI) in January 2015.
The European Medicines Agency (EMA) has also accepted for review a Marketing Authorisation Application (MAA) for MM-398 for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. The acceptance of the MAA marks the beginning of the review process in the European Union for MM-398 in this indication.
"The acceptance of our Marketing Authorisation Application for review by the European Medicines Agency is a positive indicator of the promise of this treatment to address a significant unmet need for patients with metastatic pancreatic cancer and the support for innovative new options," said David Meek, head of oncology, Baxalta. "We are actively advancing our plans to introduce nal-IRI following approval and look forward to extending the utility of the treatment to patients around the world."
The FDA and EMA have granted MM-398 orphan drug designation for patients with metastatic pancreatic cancer. MM-398 was granted Fast Track designation by the FDA in November 2014.
Merrimack and Baxalta have entered into an exclusive licensing agreement to develop and commercialise MM-398 outside of the United States. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialise MM-398 in Taiwan.
MM-398 (irinotecan liposome injection), also known as "nal-IRI," is a novel encapsulation of irinotecan in a long-circulating 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.
Pancreatic cancer is rare and deadly, accounting for only three per cent of all cancer cases worldwide but is the fourth leading cause of cancer death. An estimated 140,000 new cases are diagnosed every year around the world, two-thirds of which are among people aged 65 or older.
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 diagnosed with late stage disease. These patients are not candidates for surgery, instead receiving chemotherapy as the mainstay of their therapy. This contributes to the five year survival rate for all patients being less than six per cent; fewer than 20 per cent of newly diagnosed patients survive more than two years. There is no consensus on the standard of care for patients with metastatic pancreatic cancer previously treated with a gemcitabine-based therapy.