The FDA has granted orphan drug status to methylnaltrexone, a
medication that blocks the side effects of morphine without interfering
with pain relief.
The "orphan" designation provides special tax and other
potential benefits to sponsors for research attempting to develop
drugs to treat rare diseases. It is designed to encourage research
and testing of drugs that may be clinically useful but are not
likely to attract the interest of pharmaceutical companies because
the costs of development and distribution may exceed anticipated
revenues from sales.
"Orphan drug status is a big step toward bringing this important
drug to a population of patients in need," said Michael Roizen,
md, professor and chairman of the department of anesthesia and
critical care at the University of Chicago. Roizen and colleague
Joseph Foss, md, assistant professor of anesthesia and critical
care, have done the preliminary animal and clinical testing of
UR Labs, a privately held corporation active in drug development,
has been working with the University of Chicago to develop methylnaltrexone
for use in patients with cancer pain. United States and international
patents have been filed for many indications.
Many patients with chronic pain cannot tolerate the side effects
of long-term use of opioid-based pain medications such as morphine.
These side effects include nausea and severe constipation. As
many as 40% of chronic pain patients chose to live with the pain
rather than endure the side effects.
But methylnaltrexone may make morphine more manageable. Recently
published studies from Roizen, Foss and colleagues Chun-Su Yuan
and Jonathan Moss, also from the University of Chicago, demonstrated
that methylnaltrexone can block the side effects of opioid-based
pain relievers, preventing the constipation without altering its
effects on pain.
New Drug Doesn't Cross Blood-Brain Barrier
Methylnaltrexone was invented by the late University of Chicago
pharmacologist Leon Goldberg, md, phd, to help a friend suffering
from cancer. He started with naltrexone (Trexan), an established
antiaddiction drug that blocks the effects of morphine.
Goldberg altered the drug slightly so that it continued to block
the effects of morphine throughout the body, preventing the nausea
and constipation caused by morphine. But by attaching a methyl
group to the naltrexone, he altered the molecule to prevent it
from crossing the blood-brain barrier. As a result, it did not
interfere with morphine's effect on pain, which is centered in
Despite encouraging results in animal models and early trials
in human volunteers, no pharmaceutical company has yet been willing
to 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 group
of users, fewer than 200,000 people, it can be difficult for the
manufacturer to recoup that investment. Orphan-drug status radically
improves the odds of bringing such drugs into use."
Phase II-III trials of methylnaltrexone, which test how well the
drug works and how it compares to alternative medications, will
begin at the University of Chicago Hospitals Clinical Research
Center and a hospice in Great Britain this year.