Wyeth Pharmaceuticals, a division of Wyeth, and Progenics Pharmaceuticals, Inc. announced their plans for the further development of methylnaltrexone. Methylnaltrexone is an investigational drug that is being studied as a treatment for the peripheral side effects of opioid analgesics, without interfering with pain relief.

Methylnaltrexone is being developed in three dosage forms: subcutaneous and oral forms as treatment platforms for opioid induced-bowel dysfunction, and an intravenous form for post operative bowel dysfunction. In December 2005, Wyeth and Progenics Pharmaceuticals entered into a collaboration to develop and commercialize methylnaltrexone.

"In the five months that Wyeth and Progenics have been working together on methylnaltrexone, we have significantly advanced its clinical, regulatory and commercial development," said Robert R. Ruffolo, Jr., Ph.D., President, Wyeth Research and Senior Vice President, Wyeth. "The collaboration has been working with agility and speed, making important progress in shaping the clinical development of all three forms of methylnaltrexone. Opioid-induced and post-operative bowel dysfunctions represent serious medical needs for which there are currently no approved prescription therapies. As methylnaltrexone achieves clinical and regulatory milestones, we plan to communicate our progress regularly."

Opioid analgesics such as morphine are widely used to treat patients with moderate to severe pain. However, opioid use often results in Opioid-induced bowel dysfunction (OBD), a combination of symptoms including constipation, nausea, abdominal discomfort, bloating and loss of appetite. OBD occurs when opioids bind to mu-opioid receptors in the gut, reducing gastrointestinal motility. The consequences are not only distressing, but may be severe enough to interfere with adequate pain control.

Progenics Pharmaceuticals has completed two phase 3 clinical trials in advanced illness patients with OBD using a subcutaneous form of methylnaltrexone. In early 2007, the companies plan to submit a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for this indication. If the NDA is approved, Wyeth plans a United States market launch soon thereafter. Following the United States submission, Wyeth plans to complete regulatory filings in Europe and the rest of the world for subcutaneous methylnaltrexone.

Approximately 1.7 million patients in the United States have terminal diseases such as advanced cancer, cardiopulmonary disease or AIDS, some of whom receive opioids for pain control. For those who develop OBD, there is an important unmet medical need. Laxatives and stool softeners are often ineffective in relieving the constipation that is part of OBD, and do not address the other symptoms of OBD.

In 2006, Progenics and Wyeth plan to initiate studies of subcutaneous methylnaltrexone in patients with OBD other than those with advanced illness.

Progenics conducted a phase 2 study of intravenous methylnaltrexone in patients who had undergone segmental colectomies. In 3Q 2006, Progenics plans to initiate a United States pivotal phase 3 study in patients at high risk for developing post operative bowel dysfunction (POBD), and Wyeth plans to initiate additional studies abroad. An NDA submission is planned for the intravenous form of methylnaltrexone in late 2007 or early 2008.

POBD is a major contributor to prolonged hospital stays and therefore represents an important cause of increased health care costs. Because many post-operative patients might not tolerate oral medications,intravenous methylnaltrexone could be an important for these subjects.

Progenics has completed two phase 1 clinical studies of oral methylnaltrexone in healthy volunteers. Wyeth is also conducting an ascending multiple dose oral study to examine the safety, tolerability, and pharmacokinetics of methylnaltrexone in healthy subjects, which began earlier this year using an improved formulation of oral methylnaltrexone developed by Wyeth. Global pivotal clinical studies for the oral formulation will be conducted by Wyeth and will begin in 3Q 2006. Wyeth has primary responsibility for the clinical studies and regulatory filings of oral methylnaltrexone. An NDA submission is planned for the oral form of methylnaltrexone in the U.S. in late 2008 or early 2009.

There are several million patients in the United States receiving chronic opioid therapy for lower back pain, arthritis, neuropathic pain, and other painful conditions. OBD is a common side effect of opioids, which can affect health status and interfere with pain management.