Cancer Pain Remedy Wins Orphan Drug Status

December 1, 1996

The FDA has granted orphan drug status to methylnaltrexone, a medication that blocks the side effects of morphine without interfering with pain relief.

The FDA has granted orphan drug status to methylnaltrexone, amedication that blocks the side effects of morphine without interferingwith pain relief.

The "orphan" designation provides special tax and otherpotential benefits to sponsors for research attempting to developdrugs to treat rare diseases. It is designed to encourage researchand testing of drugs that may be clinically useful but are notlikely to attract the interest of pharmaceutical companies becausethe costs of development and distribution may exceed anticipatedrevenues from sales.

"Orphan drug status is a big step toward bringing this importantdrug to a population of patients in need," said Michael Roizen,md, professor and chairman of the department of anesthesia andcritical care at the University of Chicago. Roizen and colleagueJoseph Foss, md, assistant professor of anesthesia and criticalcare, have done the preliminary animal and clinical testing ofthe drug.

UR Labs, a privately held corporation active in drug development,has been working with the University of Chicago to develop methylnaltrexonefor use in patients with cancer pain. United States and internationalpatents have been filed for many indications.

Many patients with chronic pain cannot tolerate the side effectsof long-term use of opioid-based pain medications such as morphine.These side effects include nausea and severe constipation. Asmany as 40% of chronic pain patients chose to live with the painrather than endure the side effects.

But methylnaltrexone may make morphine more manageable. Recentlypublished studies from Roizen, Foss and colleagues Chun-Su Yuanand Jonathan Moss, also from the University of Chicago, demonstratedthat methylnaltrexone can block the side effects of opioid-basedpain relievers, preventing the constipation without altering itseffects on pain.

New Drug Doesn't Cross Blood-Brain Barrier

Methylnaltrexone was invented by the late University of Chicagopharmacologist Leon Goldberg, md, phd, to help a friend sufferingfrom cancer. He started with naltrexone (Trexan), an establishedantiaddiction drug that blocks the effects of morphine.

Goldberg altered the drug slightly so that it continued to blockthe effects of morphine throughout the body, preventing the nauseaand constipation caused by morphine. But by attaching a methylgroup to the naltrexone, he altered the molecule to prevent itfrom crossing the blood-brain barrier. As a result, it did notinterfere with morphine's effect on pain, which is centered inthe brain.

Despite encouraging results in animal models and early trialsin human volunteers, no pharmaceutical company has yet been willingto make a long-term commitment to developing methylnaltrexone.

"The costs of developing a new drug can be astronomical,"said Roizen. "For a medication targeted to only a small groupof users, fewer than 200,000 people, it can be difficult for themanufacturer to recoup that investment. Orphan-drug status radicallyimproves the odds of bringing such drugs into use."

Phase II-III trials of methylnaltrexone, which test how well thedrug works and how it compares to alternative medications, willbegin at the University of Chicago Hospitals Clinical ResearchCenter and a hospice in Great Britain this year.