ONIVYDE (formerly known as nal-IRI, MM-398 and PEP02) is a proprietary liposome encapsulation of irinotecan, a topoisomerase 1 inhibitor. And Irinotecan HCl (Camptosar®) is a broad spectrum anti-cancer cytotoxic drug approved for the treatment of colorectal cancer.
PharmaEngine licensed the Asian (2003) and European (2005) development, manufacturing and commercialization rights of ONIVYDE from Hermes Biosciences, Inc., South San Francisco, CA. (In 2009, Hermes was acquired by Merrimack Pharmaceuticals, Inc., Cambridge, MA.) In 2011, after completed preclinical, Phase 1 and 2 clinical studies, PharmaEngine licensed the European and Asian rights except for Taiwan, to Merrimack. During 2011 to 2014, Merrimack sponsored a global phase 3 NAPOLI-1 study in metastatic pancreatic cancer patients. In 2014, the positive top line data of this study led Merrimack to grant the license of ONIVYDE outside of the U.S. and Taiwan to Baxter International Inc. (NYSE: BAX), which was then spun off as Baxalta (NYSE: BXLT) in 2015.
In June 2015, following the new drug applications Submission to the U.S. FDA in April, ONIVYDE was granted the Priority Review Designation. In May 2015, Baxalta and PharmaEngine also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) and an NDA to the Taiwan FDA, respectively. Consequently, ONIVYDE was granted orphan drug, fast track and priority review status by the U.S. FDA, as well as orphan drug designation and acceptance for review by the EMA. In October 2015, ONIVYDE was approved by the US FDA and the TFDA, and under MAA review by the EMA.
After completion of several preclinical and clinical studies, ONIVYDE, has been approved in the treatment of pancreatic cancer. The approved indication of ONIVYDE is pancreatic cancer. Clinical trials are ongoing in other indications. So far, four different phase 1 and three phase 2 trials have been completed. Phase 2 studies in gastric, pancreatic and colorectal cancer were presented at the 2011 ASCO GI, 2011 ASCO Annual Meetings and 2015 ASCO GI.
In January 2012, Merrimack initiated a pivotal Phase 3 clinical trial of ONIVYDE (MM-398) for the treatment of patients with metastatic pancreatic cancer who have previously failed treatment with gemcitabine. This study is referred to as NAPOLI-1 (NAPOLI acronym: NAnoliPOsomaL Irinotecan). The primary endpoint was overall survival. Study sites included North America, the European Union, Latin America, Australia and Asia (including Taiwan). The Global Principal Investigator was Daniel von Hoff, M.D., F.A.C.P. of TGen, University of Arizona, Mayo Clinic and Scottsdale Healthcare. NAPOLI-1 was a randomized, open label Phase 3 study in patients with metastatic pancreatic cancer who received prior gemcitabine-based therapy. The study evaluated two ONIVYDE regimens, 80 mg/m2 combined with 5-fluorouracil (5-FU) and leucovorin (LV) every two weeks, and 120 mg/m2 as a monotherapy every three weeks. Each arm was compared to a control arm of 5-FU and LV. A total of 417 patients were randomized across the three arms. Each ONIVYDE regimen was compared against the control arm on the primary endpoint of overall survival. Patients were enrolled at 76 sites of the 105 sites initiated in North America, South America, Europe, Asia and Australia. In January, 2015, the expanded analyses presented at 2015 ASCO GI further corroborated the top line data presented at the ESMO GI 2014 on achieving overall survival improvement.
The recent updated overall survival analysis of the Phase 3 NAPOLI-1 study of ONIVYDE in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival in patients with post-gemcitabine metastatic pancreatic adenocarcinoma when compared to 5-FU and leucovorin alone. These data was presented at the American Society of Clinical Oncology 2016 Gastrointestinal Cancers Symposium (ASCO GI). Updated findings showed one in four patients treated with ONIVYDE survived a milestone of one year or more: 12-month overall survival estimates of 26% (95% CI, 18-35%) for ONIVYDE in combination with 5-FU and leucovorin, a 63% improvement when compared to 16% (95% CI, 10-24%) for 5-FU and leucovorin alone.
ONIVYDE is the first drug approved for treating pancreatic cancer patients who have failed the first-line treatment. Pancreatic cancer is a highly malignant disease with patients usually diagnosed at an advanced stage. It is the fourth leading cause of death, with about 45,000 patients dying of this disease in the U.S. every year. In Taiwan, pancreatic cancer is also responsible for about 1,700 deaths every year. The global standard first line treatment is a gemcitabine (Gemzar®) based regimen in combination with erlotinib (Tarceva®) or paclitaxel albumin-stabilized nanoparticles (Abraxane®).
ONIVYDE targets indications include pancreatic, gastric, colorectal, lung, and brain cancers. Completed clinical data shows that it has the potential to become a better drug than irinotecan, especially as a good backbone in combination with targeted therapies. The estimated market size is over USD1 billion worldwide.
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