Merrimack Pharmaceutical Submits New Drug Application for MM-398 in Metastatic Pancreatic Cancer

Commentary by: Julie Fleshman, President and CEO of the Pancreatic Cancer Action Network

Merrimack Pharmaceuticals, Inc., has submitted a New Drug Application (NDA) for MM-398 (irinotecan liposome injection) in the treatment of patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. Merrimack has requested a priority review of the NDA.

“The options for treatment of metastatic pancreatic cancer are few, and the recent advance of the addition of nab-paclitaxel to the previous standard-of-care gemcitabine demonstrates an overall survival of less than 9 months,” said Lynn M. Matrisian, PhD, MBA, Vice President, Scientific & Medical Affairs, Pancreatic Cancer Action Network.  “Many patients need to pursue several options during the course of treatment, and if approved, this will be the first drug combination that is FDA-approved for second-line treatment for metastatic pancreatic cancer,” Dr. Matrisian said.

MM-398 was granted an orphan drug designation by the U.S. Food and Drug Administration (FDA) for patients with metastatic pancreatic cancer, and was granted Fast Track designation in November 2014 for the treatment of patients with metastatic adenocarcinoma of the pancreas who previously were treated with gemcitabine-based therapy.

MM-398, also known as nal-IRI, is a nanoliposomal formulation of irinotecan encapsulated in a lipid sphere. In tumor cell models, this nanoliposomal technology was found to alter the pharmacokinetic properties of irinotecan, increasing the retention time and exposure to SN-38—the active form of the drug. SN-38 functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death.

Greater Overall Survival Found with MM-398–Based Therapy
The New Drug Application is based on the results of the international phase 3 study NAPOLI-1 conducted in patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. Patients given MM-398 in combination with 5-fluorouracil (5-FU) and leucovorin had a significantly longer overall survival (the primary outcome) as well as significantly longer progression free survival and greater overall response rate compared patients who received 5-FU and leucovorin alone (Table). The most common Grade 3 or higher adverse events in patients receiving MM-398 and 5-FU/LV were neutropenia, fatigue, and gastrointestinal effects. Monotherapy with MM-398 was not linked to significant improvements in these outcomes compared with the control arm of 5-FU and leucovorin.

“This demonstration of a survival benefit from the MM-398 plus 5-FU and leucovorin combination is particularly important given that we have very few treatment options for patients in this tough clinical setting,” said global principal investigator of the NAPOLI-1 study Daniel D. Von Hoff, MD, FACP, Chief Scientific Officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center, Scottsdale, AZ, and Distinguished Professor at Translational Genomics Research Institute (TGen), Phoenix, AZ.

MM-398 May Improve Treatment Landscape for Pancreatic Cancer
“The Pancreatic Cancer Action Network’s goal is to double pancreatic cancer survival by 2020. The positive results of this trial demonstrate progress toward that goal in a disease for which additional treatment options are urgently needed to improve patient outcomes,” said Julie Fleshman, President and CEO of the Pancreatic Cancer Action Network. “Though we always hope for momentous solutions to treat pancreatic cancer, we are encouraged by any type of progress. We know that any new developments will eventually lead to even greater treatment advances, and also underscore the important role clinical trials play when patients are exploring their treatment options. We applaud Merrimack’s dedication to improving the treatment landscape for this patient population, and helping us charge forward in the fight against pancreatic cancer,” Ms. Fleshman said.

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