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Genetically engineered protein useful in treating severe ulcerative colitis
CHAPEL HILL - A genetically engineered protein called visilizumab produced long-lasting clinical benefits for people with the most severe form of ulcerative colitis who took part in a clinical trial led by a University of North Carolina at Chapel Hill researcher.
Dec. 13, 2007
Genetically engineered protein useful in treating severe ulcerative colitis
CHAPEL HILL - A genetically engineered protein called visilizumab produced long-lasting clinical benefits for people with the most severe form of ulcerative colitis who took part in a clinical trial led by a University of North Carolina at Chapel Hill researcher.
Forty-five percent of patients in the study who were treated with visilizumab – an investigational drug also known by the brand name Nuvion – did not need medical or surgical salvage therapies during the first year after treatment.
This finding is preliminary and additional research is needed, but it offers a ray of hope to approximately 500,000 people in the U.S. who suffer from ulcerative colitis, said Dr. Scott Plevy, an associate professor of medicine, microbiology and immunology in the UNC School of Medicine and lead author of the study, which is published in the November 2007 issue of the journal Gastroenterology.
“The patients in this study were people for whom all other standard medical therapies had failed and they were so severely ill they had to be hospitalized,” Plevy said. “Historically, almost all patients in this group will ultimately require surgery to remove their large intestine. So to find a drug that can prevent the need for surgery for is an encouraging development.”
Ulcerative colitis is a disease that causes inflammation and sores, called ulcers, in the lining of the rectum and colon. Ulcers form where inflammation has killed the cells that usually line the colon, then bleed and produce pus. Inflammation in the colon also causes the colon to empty frequently, causing diarrhea.
These problems are believed to be caused by an over-active immune system response within the colon, Plevy said, and the “bad actors” in this process are known as CD3 antigen-positive T cells. So, newer biologic therapies for ulcerative colitis that are aimed at inhibiting the activation and proliferation of these T-cells are considered to be an attractive therapeutic approach.
Plevy said he and his co-researchers believed that visilizumab might be an effective therapy for severe steroid-refractory ulcerative colitis because it specifically binds to CD3 proteins that are expressed on T cells and thus has an inhibiting effect. Similar genetically engineered proteins had previously been shown to be helpful in preventing rejection of transplanted organs in transplant patients and in the treatment of diabetes, Plevy said.
In the study, 32 patients were given intravenous infusions of visilizumab on 2 consecutive days. Eight patients started with a dose of 15 micrograms per kilogram of body weight. Because of negative side effects at this dose – such as a drop in blood pressure, fever, nausea and vomiting – the dose was reduced to 10 micrograms for all patients for the rest of the study. At the lower dose, side effects were found to be within acceptable limits.
Thirty days after receiving the treatment, 85 percent of the patients showed clinical improvement. Of these, 41 percent achieved clinical remission (absence of all symptoms) and 44 percent achieved endoscopic remission (complete healing of the lining of the colon). Most significantly, 45 percent did not require salvage therapies – such as surgical removal of the large intestine – during the first year after being treated with visilizumab.
Plevy and colleagues concluded that visilizumab had an acceptable safety profile at the 10 microgram dose, may be clinically beneficial for patients with severe steroid-refractory ulcerative colitis and merits further exploration in additional clinical trials.
The drug used in this study is manufactured by PDL BioPharma of Redwood City, Calif. The company’s executive vice president and chief scientific officer, Richard Murray, earned his Ph.D. in microbiology and immunology from the UNC School of Medicine in 1988.
Media contact: Stephanie Crayton, (919) 966-2860 or scrayton@unch.unc.edu
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