The FDA Department of Orphan Products Development has granted orphan drug designation to demcizumab (anti-DLL4, OMP-21M18), which is currently in a phase Ib clinical trial in combination with AbraxaneÂ® (nab-paclitaxel) and gemcitabine.
The US Food and Drug Administration (FDA) Department of Orphan Products Development has granted orphan drug designation to demcizumab (anti-DLL4, OMP-21M18), which is currently in a phase Ib clinical trial in combination with Abraxane® (nab-paclitaxel) and gemcitabine in the first-line setting for patients with stage IV pancreatic cancer.1
Demcizumab is part of OncoMed Pharmaceuticals Inc’s collaboration with Celgene Corporation.
"We are very pleased that the FDA designated demcizumab as an orphan drug for the treatment of pancreatic cancer, which is a major unmet medical need,” said Paul J. Hastings, chairman and chief executive officer of OncoMed in a press release.
According the American Cancer Society, pancreatic cancer is now the fourth-leading cause of cancer-related death. The majority of patients with pancreatic cancer are diagnosed after their cancer has spread locally and/or metastasized to distant organs. The average life expectancy after the diagnosis of metastatic pancreatic cancer is 3 to 6 months.
“Based on the encouraging safety and response data achieved to date for demcizumab in OncoMed's phase Ia and Ib clinical studies, we anticipate advancing demcizumab into a randomized phase II clinical study in combination with Abraxane and gemcitabine in first-line pancreatic cancer in 2014," Hastings said.
The phase I study2will test the safety of demcizumab at different dose levels when given with gemcitabine +/- Abraxane® and the effects, both positive and negative, that it has on participants. Single-agent gemcitabine was historically a standard treatment for pancreatic cancer for many years.3However, data released at the 2013 ASCO Gastrointestinal Cancers Symposium demonstrated that gemcitabine plus Abraxane® may be superior to gemcitabine alone, thus this combination may become the new standard therapy for pancreatic cancer.4
Demcizumab is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Blockade of DLL4 has shown potent anti-tumor activity in preclinical models.5Demcizumab may block the growth of cancer stem cells, the remaining tumor cells, and it may also prevent the growth of new blood vessels that tumors need to grow and spread. Although demcizumab has been administered with gemcitabine to cancer patients, it has not been given in combination with gemcitabine and Abraxane®; therefore this study will evaluate the outcomes of that combination.
Demcizumab is also being studied in a second phase Ib trial in combination with standard-of-care carboplatin and pemetrexed (Alimta) for patients with first-line advanced non-small cell lung cancer. In addition, a phase Ib/II trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is ongoing.