Date: 2016-10-18
Type of information: Granting of a Market Authorisation in the EU
Product name: Onivyde® - MM-398
Compound: nanoliposomal irinotecan injection
Therapeutic area: Cancer - Oncology
Action mechanism: topoisomerase I inhibitor. Onivyde® - MM-398 (irinotecan liposome injection) is a nanoliposomal encapsulation of the chemotherapeutic irinotecan. MM-398 has demonstrated extended circulation in comparison to free irinotecan in the clinical setting. 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. In 2014, Merrimack and Baxter International's biopharmaceutical business (Baxalta) entered into an exclusive licensing agreement to develop and commercialize MM-398 outside of the United States and Taiwan. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize MM-398 in Taiwan. Merrimack markets Onivyde® in the United States. In June 2016 Shire completed its combination with Baxalta. Through the combination, Shire gained an oncology portfolio including Oncaspar® (pegaspargase), a marketed biologic treatment for acute lymphocytic leukemia, and late-stage, partnered products such as pacritinib, an investigational oral kinase inhibitor for the treatment of patients with myelofibrosis, and Onivyde® (irinotecan liposome injection) for the treatment of patients with metastatic pancreatic cancer. Shire is responsible for the development and commercialization of Onivyde® - outside of the United States and Taiwan.
Company: Merrimack Pharmaceuticals (USA - MA) Shire (UK - USA)
Disease: patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy
Latest news: * On October 18, 2016, Shire announced that the European Commission (EC) has granted Marketing Authorization of Onivyde® (pegylated liposomal irinotecan hydrochloride trihydrate), also known as nal-IRI or MM-398, for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who have progressed following gemcitabine-based therapy. Onivyde® is the first and only approved treatment option for this patient population. With this approval, Shire is authorized to market Onivyde® in the 28 Member States of the European Union (EU), as well as in Iceland, Liechtenstein and Norway. Onivyde® was previously approved in the FDA in October 2015. In September 2015, the European Society of Medical Oncology (ESMO) stated that use of MM-398 (Onivyde®) when available in all countries, may be the best option for patients following gemcitabine-based therapy. The marketing authorization is based on the data from the pivotal, Phase 3 NAPOLI-1 study that demonstrated Onivyde® combined with 5-FU/LV significantly improved overall survival (OS) (primary endpoint), as well as progression-free survival (PFS) and objective response rate (ORR) relative to the 5-FU/LV control arm (secondary endpoints). In the trial, the most common Grade 3 or higher adverse events with greater than five percent difference in patients receiving ONIVYDE and 5-FU/LV, versus 5-FU/LV alone, were neutropenia, fatigue, diarrhoea, and vomiting. * On 21 July 2016, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Onivyde®, in combination with fluorouracil and leucovorin, for the treatment of metastatic adenocarcinoma of the pancreas. Onivyde® will be available as a concentrate for solution for infusion (5.0 mg/ml). When added to 5-fluorouracil (5-FU) 2,400 mg/m2 and leucovorin (LV) 400 mg/m2, Onivyde® improved survival compared with 5-FU 2,000 mg/m2 and LV 200 mg/m2. The most common side effects are diarrhoea, nausea, vomiting, decreased appetite, neutropenia, fatigue, asthenia, anaemia, stomatitis and pyrexia. * On January 7, 2016, Baxalta announced that Health Canada has granted Priority Review status for its New Drug Submission (NDS) for irinotecan liposome injection (nal-IRI). Baxalta is seeking marketing approval of nal-IRI from Health Canada for the treatment of patients with metastatic adenocarcinoma of the pancreas previously treated with gemcitabine-based therapy. Priority Review allows for expedited review of critical new drugs faster than the standard timeline. Review by Health Canada is expected to be conducted in the second half of 2016. The application is based upon the results of an international Phase 3 study (NAPOLI-1) conducted among patients with metastatic pancreatic cancer (mPaC) who previously received gemcitabine-based therapy. In combination with 5-fluorouracil (5-FU) and leucovorin (LV), nal-IRI 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 LV. The most common Grade 3 or higher adverse events in patients receiving nal-IRI and 5-FU/LV were neutropenia, fatigue and gastrointestinal effects. This was the first global Phase 3 study in a post-gemcitabine setting to demonstrate a survival benefit in the treatment of this aggressive disease. Baxalta and Merrimack recently enrolled the first patient in an exploratory Phase 2 clinical study of nal-IRI in previously untreated, metastatic pancreatic adenocarcinoma to assess the safety and efficacy of the combination of nal-IRI, 5-FU and LV, with or without the addition of oxaliplatin, versus nab-paclitaxel and gemcitabine. Based on the current design of this study, data is expected in the first half of 2017. In addition to studying nal-IRI in patients with pancreatic cancer, there are ongoing Phase 1 studies of nal-IRI in patients with pediatric sarcoma, glioma, breast and gastric cancer. * On October 22, 2015, the FDA approved Onivyde® (irinotecan liposome injection), in combination with fluorouracil and leucovorin, to treat patients with advanced (metastatic) pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy. The FDA granted Priority Review and orphan drug designations for Onivyde®. The effectiveness of Onivyde® was demonstrated in a three-arm, randomized, open label study of 417 patients with metastatic pancreatic adenocarcinoma whose cancer had grown after receiving the chemotherapeutic drug gemcitabine or a gemcitabine-based therapy. The study was designed to determine whether patients receiving Onivyde® plus fluorouracil/leucovorin or Onivyde alone lived longer than those receiving fluorouracil/leucovorin. Patients treated with Onivyde® plus fluorouracil/leucovorin lived an average of 6.1 months, compared to 4.2 months for those treated with only fluorouracil/leucovorin. There was no survival improvement for those who received only Onivyde compared to those who received fluorouracil/leucovorin. In addition, patients receiving Onivyde plus fluorouracil/leucovorin had a delay in the amount of time to tumor growth compared to those who received fluorouracil/leucovorin. The average time for those receiving Onivyde plus fluorouracil/leucovorin was 3.1 months compared to 1.5 months for those receiving fluorouracil/leucovorin. The safety of Onivyde® was evaluated in 398 patients who received either Onivyde with fluorouracil/leucovorin, Onivyde alone or fluorouracil/leucovorin. The most common side effects of treatment with Onivyde included diarrhea, fatigue, vomiting, nausea, decreased appetite, inflammation in the mouth (stomatitis) and fever (pyrexia). Onivyde was also found to result in low counts of infection-fighting cells (lymphopenia and neutropenia). Death due to sepsis following neutropenia has been reported in patients treated with Onivyde®. The labeling for Onivyde i®ncludes a boxed warning to alert health care professionals about the risks of severe neutropenia and diarrhea. Onivyde is not approved for use as a single agent for the treatment of patients with metastatic pancreatic cancer. * On May 4, 2015, Baxter and Merrimack Pharmaceuticals jointly announced that Baxter has submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for approval of MM-398 (irinotecan liposome injection), also known as ''nal-IRI,'' an investigational treatment for patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. The submission follows Merrimack's recent filing of a new drug application (NDA) for this indication with the FDA. Both the U.S. and European submissions were based on the positive results of the international Phase 3 NAPOLI-1 study, which was conducted among patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. MM-398 in combination with 5-fluorouracil (5-FU) and leucovorin (LV) achieved its primary and secondary endpoints by demonstrating a clinically and 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 LV. 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. The data were presented in June 2014 . * On November 19, 2014, Merrimack Pharmaceuticals announced that the FDA has granted MM-398 (nanoliposomal irinotecan injection), also known as ''nal-IRI,'' Fast Track designation for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. Merrimack is currently preparing a New Drug Application (NDA) for MM-398 in the United States for the treatment of patients with metastatic pancreatic cancer previously treated with a gemcitabine-based therapy. Fast Track designation allows sections of the NDA to be submitted to the FDA as they are completed. Based upon this designation, Merrimack expects to initiate the NDA submission in 2014 with the goal of completing the NDA submission late in the first quarter or early in the second quarter of 2015.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE: 2015-05-04
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-10-22
UE authorization: 2016-10-18
Favourable opinion UE: 2016-07-21
Favourable opinion USA:
Orphan status USA: 2011-07-21
Orphan status UE: 2011-12-09
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
