Merrimack Pharmaceuticals said today its nanotherapeutic drug candidate MM-398 (irinotecan liposome injection), combined with 5-fluorouracil (5-FU) and leucovorin, met its primary endpoint of overall survival in a Phase III trial of in patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy.
Merrimack said it would submit a New Drug Application (NDA) for the combination to the FDA later this year based on the results of the nanoliposomal irinotecan (NAPOLI-1) Phase III study. Those results showed in part that the combination achieved an overall survival of 6.1 months, compared with survival of 4.2 months for the control arm of 5-FU and leucovorin.
NAPOLI-1 also showed a statistically significant advantage for progression free survival among patients treated with the combination, Merrimack added, without disclosing details.
NAPOLI-1 also examined MM-398 as a monotherapy, where it achieved a median overall survival period of 4.9 months—but did not generate a statistically significant survival advantage over the 4.2 months recorded for patients in the control arm. Worse, monotherapy patients generally experienced a higher level of adverse events compared to patients who received the combination of MM-398 with 5-FU and leucovorin.
The company said it will present detailed study results next month at the European Society for Medical Oncology World Conference on Gastrointestinal Cancer, to be held June 25-28 in Barcelona, Spain.
"Given that there have only been a handful of successful Phase 3 trials in pancreatic cancer in the past 25 years, it is gratifying to have the first positive Phase 3 trial in the post-gemcitabine setting. The results reinforce our confidence in our entire nanoliposomal pipeline,” Robert Mulroy, Merrimack’s president and CEO, said in a statement.
MM-398, also known as "nal-IRI," consists of the chemotherapeutic irinotecan, encapsulated in a liposomal sphere. 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.
"Our research suggests an opportunity to develop MM-398 in multiple indications," Merrimack states on its website. The company is evaluating MM-398 in additional trials for its ability to treat chemotherapy-resistant tumors across multiple types of cancers, including pancreatic, lung, colorectal, and glioma
The FDA and European Medicines Agency in 2011 granted orphan drug designations to MM-398 in metastatic pancreatic cancer. The company also says it is developing an imaging diagnostic and using its network biology approach to simultaneously develop biopsy-based assays, both of which are designed to help identify patients most likely to respond to MM-398 treatment.
Merrimack’s pipeline includes another nanotherapeutic, MM-302, which consists of the chemotherapeutic doxorubicin encapsulated in a liposomal sphere. The compound is designed to fight breast cancer by attacking HER2 overexpressing cancer cells while minimizing exposure to healthy tissues such as the heart. MM-302 is the subject of a Phase I clinical study for patients with HER2+ breast cancer.
The company hopes its nanotherapeutics like MM-398 will perform better than its MM-121 (SAR256212) monoclonal antibody, developed in collaboration with Sanofi. MM-121 failed to meet its endpoints in three trials last year, although it showed more promising results in subpopulations such as patients with specific biomarkers.
Merrimack will present Phase II data later this year at the annual meeting of the American Society of Clinical Oncology in Chicago, the company said in a separate statement announcing its first-quarter results. Merrimack trimmed its quarterly net loss to $27.8 million, compared with the Q1 2013 net loss of $28.3 million.