PharmaEngine announced that the additional analyses from the global phase 3 NAPOLI-1 study of MM-398 (PEP02, liposome irinotecan injection) in metastatic pancreatic cancer were presented by Li-Tzong Chen, MD in an oral session at the American Society of Clinical Oncology 2015 Gastrointestinal Cancers Symposium (ASCO GI) on January 16, 2015. This phase 3 NAPOLI-1 study was sponsored by PharmaEngine’s partner, Merrimack Pharmaceuticals, PharmaEngine retains the rights to commercialise MM-398 in Taiwan.

The primary analysis of the NAPOLI-1 phase 3 trial, presented at ESMO GI 2014 in Barcelona, Spain last year, demonstrated a statistically significant increase in overall survival with an unstratified hazard ratio of 0.67 (95 per cent CI [0.49-0.92], p = 0.0122) and a median of 6.1 months for the combination of MM-398 plus 5-FU/LV compared to 4.2 months in the 5-FU/LV control arm.

The expanded analyses presented at 2015 ASCO GI further corroborate the top line data presented at the ESMO GI 2014 on achieving the primary endpoint of overall survival for the treatment with MM-398, 80 mg/m2 in combination with 5-FU/LV every two weeks in metastatic pancreatic cancer previously treated with gemcitabine-based therapy.

Summary results from NAPOLI-1 phase 3 trial presented at ASCO GI 2015:

In the stratified analysis, which accounts for pre-specified prognostic factors included in the study randomisation stratification, the overall survival for MM-398 in combination with 5-FU/LV compared to control arm resulted in a hazard ratio of 0.57 (95 per cent CI [0.41-0.80], p = 0.0009).

    In the Per Protocol population (defined by patients who received 80 per cent of protocol defined dose and were able to remain on treatment for at least 6 weeks), MM-398 in combination with 5-FU/LV demonstrated superior overall survival and tumor control to the control arm of 5-FU/LV alone. In the Per Protocol analysis, median overall survival for the combination therapy arm was 8.9 months versus 5.1 months in the control arm (stratified HR = 0.47, 95 per cent CI [0.29-0.77], p = 0.0018).

The significant improvement was also observed in PFS (overall and at 3 months), objective response rate and CA19-9 tumour marker response for MM-398 in combination with 5-FU/LV.

“On behalf of the global study team, I am privileged to present the expanded analyses of NAPOLI-1 study at the ASCO GI 2015. Such additional analyses further demonstrate the robust survival benefits of the MM-398/5-FU/LV combination in the metastatic pancreatic cancer patients in the post-gemcitabine setting, and this regimen also showed a favorable safety profile,” said Prof. Li-Tzong Chen, MD, Director, Investigator and Attending Physician at the National Institute of Cancer Research, National Health Research Institutes in Taiwan.

NAPOLI-1 (NAnoliPOsomaL Irinotecan) is a randomised, open label phase 3 study in patients with metastatic pancreatic cancer who received prior gemcitabine-based therapy. The study evaluated two MM-398 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 randomised across the three arms. Each MM-398 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.

MM-398 (PEP02, liposome irinotecan injection or nal-IRI) is a novel, stable nanotherapeutic encapsulation of the marketed chemotherapy drug irinotecan. In May 2011, PharmaEngine and Merrimack executed an exclusive license agreement. Under the terms of the agreement, PharmaEngine granted back Merrimack the rights to develop, manufacture, and commercialize PEP02 (designated as MM-398 by Merrimack) in Asia and Europe, and retained the same rights in Taiwan. In September of 2014, Merrimack licensed the rights to MM-398 outside of the US and Taiwan to Baxter (NYSE:BAX). In 2011, MM-398 has separately received orphan drug designation from the US FDA and European Medicines Agency (EMA) for the treatment of pancreatic cancer. In addition, MM-398 received Fast Track Designation for post-gemcitabine metastatic pancreatic cancer from the US FDA in November 2014. PharmaEngine, Merrimack and Baxter are preparing the regulatory submissions of New Drug Applications or Marketing Authorisation Application to TFDA, US FDA, and EMA, respectively.