Methylnaltrexone, a drug developed to relieve one of the major side effects of pain therapy for cancer patients, has received marketing approval from Health Canada, the Canadian Regulatory Agency, for subcutaneous use in the treatment of opioid-induced constipation in patients with advanced illness receiving palliative care.
Health Canada's decision regarding methylnaltrexone (to be marketed as RELISTORTM) marks the first regulatory approval of this novel medication anywhere in the world. A decision from the United States Food and Drug Administration is expected before summer.
Methylnaltrexone was invented in 1979 by the late University of Chicago pharmacologist Leon Goldberg.To help a dying friend with morphine-induced constipation, Goldberg took naltrexone, an established drug that blocks the effects of morphine, and altered it slightly so that it could no longer cross the protective barrier that surrounds the brain.
onsequently, it did not interfere with morphine's effect on pain, which is centered in the brain, but it did block morphine's effects on the bowels, which are mediated by receptors in the gastrointestinal tract.
Initial success in this compassionate-use setting drew the notice of Goldberg's university colleagues Jonathan Moss, Chun-Su Yuan and others who continued, after Goldberg died, to develop the compound -- testing it in animals, completing the initial human safety trials, performing the early clinical studies in volunteers and patients, and extending the series of drug patents.
"It took many years but it finally seems that a very interesting and useful drug will at last become an option for those who need it," said Jonathan Moss, M.D., Ph.D., professor of anesthesia & critical care at the University of Chicago and an authority on the drug's history and biological activity."Patients who depend on opiates for pain relief at the end of life are often forced to curtail their opiates because of the constipation they cause. This solves an important clinical problem for some of our most vulnerable patients."
Powerful opioid-based pain relievers -- such as Percocet, OxyContin or morphine - are taken by more than 1.5 million people suffering from advanced illness such as cancer. Although morphine and related compounds remain the gold standard for pain relief, these opioids often produce significant side effects, including severe constipation, which can be so distressing that many patients discontinue their pain medication.
In 2001, Progenics Pharmaceuticals, Inc., of Tarrytown, NY, bought the rights to develop methylnaltrexone from the University of Chicago. In December 2005, Progenics entered into an exclusive, worldwide agreement with Wyeth Pharmaceuticals for the joint development and commercialization of methylnaltrexone for the treatment of opioid-induced side effects, including constipation and post-operative bowel dysfunction.
Since then, ongoing studies by Moss and others have uncovered several unanticipated applications for this promising drug.Moss and colleagues showed, for example, that methylnaltrexone can block the increases in HIV entry and replication that occur when immune cells are exposed to therapeutic doses of morphine. More recent studies suggest it may also be useful in treating other side effects of opioids.
Methylnaltrexone is "the first approved therapy in a new class of drugs designed to relieve one of the significant side effects of opioids on the gastrointestinal tract without interfering with their ability to provide pain relief, noted Wyeth and Progenics in a press release.
Wyeth expects that this product will be launched and available to patients in Canada within approximately 60 days.
"We now await a decision from the U.S. Food and Drug Administration by the end of April on RELISTOR," added Paul J. Maddon, M.D., Ph.D., founder, chief executive officer and chief science officer of Progenics Pharmaceuticals, Inc. "In addition, we and Wyeth continue to work with the European and Australian regulatory authorities to expand the availability of RELISTOR."
