Wyeth Pharmaceuticals, a division of Wyeth, and Progenics Pharmaceuticals, Inc. announced that Wyeth has submitted a marketing application to the Therapeutic Goods Administration (TGA) division of the Australian Government. If approved, the companies would be authorized to market the subcutaneous formulation of methylnaltrexone in Australia for the treatment of opioid-induced constipation (OIC).
Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that is designed to treat OIC without interfering with pain relief. A New Drug Application for the subcutaneous formulation of methylnaltrexone was submitted by Progenics to the US Food and Drug Administration in March 2007, and a Marketing Authorization Application was submitted by Wyeth to the European Medicines Agency in May 2007.
The application submitted in Australia is based on the US and EU regulatory submissions, and includes results from two phase 3 studies that evaluated the safety and efficacy of the subcutaneous formulation of methylnaltrexone in the treatment of OIC in patients with advanced illness receiving palliative care. All of the primary efficacy end points were positive and statistically significant, and the therapy generally was well tolerated in these studies. After being accepted for evaluation, the TGA has 255 working days to review the application.
Opioid analgesics are commonly prescribed to manage pain in patients receiving palliative care but can frequently cause constipation. There currently is no approved medication that specifically targets the underlying cause of OIC to relieve constipation in this patient population.
Opioids provide pain relief by interacting with specific opioid receptors located in the central nervous system (CNS) - the brain and the spinal cord. However, opioids also interact with the receptors outside the CNS, such as those affecting the gastrointestinal (GI) tract, altering intestinal motility and resulting in constipation that can be debilitating.
In December 2005, Wyeth and Progenics entered into an exclusive, worldwide agreement for the joint development and commercialization of methylnaltrexone for the treatment of opioid-induced side effects, including constipation and post-operative ileus (POI), a prolonged dysfunction of the GI tract following surgery. Under the terms of the collaboration, Wyeth received worldwide rights to methylnaltrexone, and Progenics retained an option to co-promote the product in the United States. The companies are collaborating on worldwide development. Wyeth has agreed to pay Progenics royalties on worldwide sales and co-promotion fees within the United States. Additionally, Wyeth is responsible for all ongoing and future development and commercialization costs.
Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that is being studied as a treatment for the peripheral side effects of opioid analgesics. It is designed to mitigate the effect of opioids on peripheral receptors without interfering with central nervous system pain relief. Methylnaltrexone is being developed in subcutaneous and oral forms to treat OIC as well as an intravenous form for the management of post-operative ileus, a prolonged dysfunction of the GI tract following surgery.
Currently, there is no approved medication that specifically targets the underlying cause of OIC to relieve constipation in this patient population. In March 2007, Progenics submitted an NDA for subcutaneous methylnaltrexone to the FDA, followed in May 2007 by the submission by Wyeth of a Marketing Authorization Application (MAA) in Europe to the European Medicines Agency (EMEA). The NDA and MAA have been accepted and validated for review by the FDA and EMEA, respectively. The FDA has set a Prescription Drug User Fee Act (PDUFA) date of January 30, 2008 to complete its review of the NDA, and completion of the MAA review by the EMEA is expected to occur in 2008.