Biotech Drug Shows Promise Against Ulcerative Colitis
Researchers also hope for benefit against Crohn's disease
By Ed Edelson
HealthDay Reporter
WEDNESDAY, June 15 (HealthDay News) -- A genetically engineered molecule has done well in a trial against ulcerative colitis, the painful disease caused by an immune system attack on the body's intestinal tissue.
A third of the patients who received daily injections of the molecule had remissions after six weeks, more than twice the rate for patents who got a placebo, according to a report in the June 16 issue of the New England Journal of Medicine.
The test is a second step in the series of trials designed to bring a drug to market, explained Dr. Nancy Simonian, senior vice president for clinical, medical and regulatory affairs at Millennium Pharmaceuticals, the biotechnology firm that created the molecule and sponsored the trial.
A lot of work needs to be done before the treatment becomes available for people with ulcerative colitis and a closely related condition, Crohn's disease, Simonian said. But there is hope that the molecule can relieve the painful symptoms of both conditions, such as bloody diarrhea, cramps and constant fatigue.
The molecule, designated MLN02, is a laboratory-produced antibody that binds to alpha4beta7, a member of a molecular family called integrins. "Integrins are important in the adhesion of inflammatory cells to cells in the body," Simonian said. "This antibody specifically blocks the migration of integrins into the intestinal tract."
That specific activity is important because any treatment that blocks a harmful activity of the immune system runs the risk of blocking beneficial activity, such as defense against infection, she explained. "Because MLN02 is very selective for the gastrointestinal tract, it reduces the risk of untoward side effects," she said.
The trial, led by physicians at Robarts Clinical Trials in London, Ontario, included 181 patients with ulcerative colitis. A third of them received daily injections of 0.5 milligrams of MLNO2 per kilogram of body weight, another third got 2 milligrams of MLNO2 per kilogram, and the final third got the placebo.
After six weeks, 32 percent of the patients getting the smaller dose of MLN02 and 33 percent of those getting the larger dose were in remission, compared to 14 percent of those who got the placebo.
What is needed now is a more extended trial with a larger number of patients that could produce the evidence required to get the drug approved for clinical practice, Simonian said.
The results of a trial of MLN02 against Crohn's disease have been less encouraging. That trial did find "a trend toward improvement," but not enough to exclude the possibility that the result was a matter of chance, she said. The improvement reached the desired statistical significance only in patients given the largest dose of the drug.
"But we are very excited about this molecule in ulcerative colitis and Crohn's disease," Simonian said.
Meanwhile, researchers at Millennium are working to produce a better version of MLN02. Development of the therapy started as a joint project with the biotechnology company Genentech, which has dropped out. Genentech gave Millennium the line of cells engineered to produce the molecule, and scientists there are trying to improve that cell line.
The differing results against ulcerative colitis and Crohn's disease could be explained by the subtle differences between the two conditions, Simonian said. "In ulcerative colitis, you get inflammation on the surface of the gut," she said. "In Crohn's disease, the inflammation goes into the wall of the intestine, which could explain why you might need different dosage schedules."
It's a "very well planned out" study, but one that needs confirmation because the number of participants was small, commented Dr. Gerald W. Dryden, Jr., assistant professor of medicine at the University of Louisville, Ky.
"It's a bit too early to tell whether significant aide effects will ultimately be seen with this medication," he said, noting that one patient in the trial had a significant immune reaction against the medication. One possible strategy would be to give drugs that reduce the immune response along with MLN02, Dryden said. |
