- ONIVYD(PEP02, MM-398, nal-IRI)

Product Backqround

ONIVYDEâ(PEP02, MM-398 and nal-IRI) is a proprietary liposome encapsulation of irinotecan, a topoisomerase 1 inhibitor. Irinotecan HCl (Camptosarâ) 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 ONIVYDEâ from Hermes Biosciences, Inc., South San Francisco, CA. (Hermes was acquired by Merrimack Pharmaceuticals, Inc., Cambridge, MA, in 2009.) In 2011, after completion of preclinical, Phase 1 and 2 clinical studies, PharmaEngine licensed the European and Asian rights excluding Taiwan to Merrimack. During 2011 to 2014, Merrimack sponsored a global phase 3 NAPOLI-1 study in metastatic pancreatic cancer patients failed on prior gemcitabine-based chemotherapy. In 2014, the positive top line data from this study led Merrimack to grant the license of ONIVYDEâ outside of the U.S. and Taiwan to Baxter International Inc. (NYSE: BAX), which biopharmaceutical division was later spun off as Baxalta (NYSE: BXLT) in 2015. Shire plc (LSE: SHP, NASDAQ: SHPG) then combined with Baxalta in June 2016.

In June 2015, following the new drug applications Submission to the U.S. FDA in April, ONIVYDEâ 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, ONIVYDEâ 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. ONIVYDEâ was approved by the US FDA and the TFDA in October 2015and received marketing authorization (MA) from European Commission (EC) in October 2016.

Clinical Development

After completion of several preclinical and clinical studies, ONIVYDEâ has been approved for pancreatic cancer patients failed on prior gemcitabine-based treatment. Clinical trials are ongoing in other indications. So far, four phase 1 and three phase 2 trials have been completed. Phase 2 studies in gastric, pancreatic and colorectal cancers 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 ONIVYDEâ (PEP02, MM-398, nal-IRI) 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 ONIVYDEâ 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 ONIVYDEâ regimen was compared against the control arm with 5-FU and LV on the primary endpoint of overall survival. A total of 417 patients were randomized across the three arms. 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 oONIVYDEâ 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 ONIVYDEâ survived a milestone of one year or more: 12-month overall survival estimates of 26% (95% CI, 18-35%) for ONIVYDEâ in combination with 5-FU and leucovorin, a 63% improvement when compared to 16% (95% CI, 10-24%) for 5-FU and leucovorin alone.

Market Forecast

ONIVYDEâ is the first drug approved for treating pancreatic cancer patients who have failed on the first-line treatment. Pancreatic cancer is a highly malignant disease with patients usually diagnosed at an advanced stage. It is the third leading cause of death, with about 43,000 patients dying of this disease in the U.S. every year. In Taiwan, pancreatic cancer is also responsible for about 1,900 deaths every year. Pancreatic cancer will overpass colorectal cancer to be the second leading cause of cancer death, just behind the lung cancer, in 2010.

New clinical indications for the future development of ONIVYDEâ include frontline pancreatic, colorectal, gastric, lung, and brain cancers. ONIVYDEâ also has the potential to provide synergistic effect of combining other novel anti-cancer agents. The market value of ONIVYDEâ cannot be overestimated.


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