Merrimack and Baxalta Announce Publication of the ONIVYDE™ (irinotecan liposome injection) NAPOLI-1 Study in The Lancet

Merrimack

and Baxalta Incorporated

today jointly announced that The Lancet has published the article "Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomized, open-label phase 3 trial" online in advance of its print issue. The Lancet is considered one of the most prestigious peer-reviewed general medical journals in the world. "The publication of the NAPOLI-1 data in The Lancet is significant, as it will provide physicians with comprehensive data on this recently approved treatment that has demonstrated improved overall survival for patients with metastatic adenocarcinoma of the pancreas who had progressed after gemcitabine-based therapy," said Prof. Li-Tzong Chen, M.D., Ph.D., corresponding author, Investigator on the NAPOLI-1 trial and Director, National Institute of Cancer Research, National Health Research Institutes in Tainan, Taiwan. "We thank the patients and their caregivers, study sites, steering committee members and the chairs for their contributions to this important study." Andrea Wang-Gillam, M.D., Ph.D., lead author of the NAPOLI-1 article and Associate Professor of Medicine, Clinical Director of GI Oncology Program, Division of Oncology, at Washington University School of Medicine, St. Louis added, "ONIVYDE in combination with fluorouracil and leucovorin extends median overall survival to six months, a 45% increase, with a well-defined safety profile in patients with metastatic adenocarcinoma of the pancreas who previously received gemcitabine-based therapy, representing a new treatment option for this patient population." The NAPOLI-1 study results were the basis of the recent U.S. Food and Drug Administration (FDA) and Taiwan FDA approval of ONIVYDE™ (irinotecan liposome injection) 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. ONIVYDE, also known as MM-398 or "nal-IRI," is the first and only FDA approved therapy in this setting. ONIVYDE is irinotecan encapsulated in liposome nanoparticles. The liposome is designed to keep irinotecan in the circulation -- sheltered from conversion to its active metabolite (SN-38) -- longer than unencapsulated irinotecan, which would increase and prolong intratumoral levels of both irinotecan and SN-38 compared with free irinotecan1. Data from the NAPOLI-1 study were previously presented at the 2014 European Society for Medical Oncology World Congress on Gastrointestinal Cancer and the American Society of Clinical Oncology 2015 Gastrointestinal Cancers Symposium. The NAPOLI-1 Study and Results1 NAPOLI-1 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. Patients were enrolled at 76 sites in North America, South America, Europe, Asia and Oceania. 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. Key findings of the study as published in The Lancet include: 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=0.012, unstratified hazard ratio for death (HR) =0.67, 95% CI: [0.49–0.92]). The monotherapy regimen in this study did not show improvement over the 5-FU and leucovorin arm: 4.9 vs 4.2 months (p=0.94, HR=0.99, 95% CI: [0.77–1.28]). ONIVYDE in combination with 5-FU and leucovorin achieved a longer progression-free survival compared with the 5-FU and leucovorin arm (3.1 months versus 1.5 months; unstratified HR=0.56 [95% CI, 0.41–0.75]). Unconfirmed objective response rate was higher in the ONIVYDE in combination with 5-FU and leucovorin arm than in the 5-FU and leucovorin arm: 16% (19/117) versus 1% (1/119) (difference 15.4 percentage points, 95% CI, 8.5-22.3; p<0.0001). The most common grade 3 or 4 adverse events that occurred more frequently in the ONIVYDE in combination with 5-FU and leucovorin arm (>2% incidence versus 5-FU and leucovorin) were neutropenia, diarrhea, vomiting, and fatigue. Baxalta Incorporated is responsible for the development and commercialization of ONIVYDE outside of the United States and Taiwan under the exclusive licensing agreement with Merrimack. In May 2015, the European Medicines Agency accepted for review Baxalta's marketing authorization application for ONIVYDE based on the same clinical results. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize ONIVYDE in Taiwan. PharmaEngine filed a New Drug Application with the Taiwan FDA on May 29, 2015, and received the approval of ONIVYDE on October 22, 2015.