Vedolizumab, a potentially new treatment for UC and Crohn's disease is being fast tracked for review by the FDA. The BLA (biologics license application) will give priority review to the ulcerative colitis application and standard review to the Crohn's disease application.
The part of the clinical trial that is most important to me is the said adverse effects that were found in the patients who participated in the study. Based on the concluding trial results, the adverse effects of the drug is said to be the same as the placebo. That's great news. I'm going to continue to watch this drug for new updates and news pertaining to safety. So far, this new treatment by Takeda Pharmaceuticals looks promising.
I have also included the clinical trial abstract below.
The part of the clinical trial that is most important to me is the said adverse effects that were found in the patients who participated in the study. Based on the concluding trial results, the adverse effects of the drug is said to be the same as the placebo. That's great news. I'm going to continue to watch this drug for new updates and news pertaining to safety. So far, this new treatment by Takeda Pharmaceuticals looks promising.
I have also included the clinical trial abstract below.
On Sept. 4, Takeda Pharmaceutical Company Ltd., announced that it received priority review status from the FDA for its drug vedolizumab, an investigational antibody for the treatment of adults with moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC). Takeda submitted a biologics license application (BLA) to the FDA in June for the treatment of CD and UC; the UC application will receive priority review, and the application for CD will be reviewed under the standard timeline.
The FDA grants priority review status for drugs that are designed to treat a serious condition, and that if approved, would provide a significant improvement in safety or effectiveness. Priority review designation allows for an eight-month review period compared with the standard 12-month review.
“The need to seek new treatment options is well recognized,” said William J. Sandborn, MD, chief, Division of Gastroenterology, and professor of medicine, University of California, San Diego School of Medicine, in a press statement. “Vedolizumab has demonstrated the potential to be another possible treatment option for people with moderately to severely active CD and UC.”
Vedolizumab is a humanized monoclonal antibody that specifically antagonizes α4β7 integrin and inhibits it from binding to its target receptor, mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. It interacts with α4β7 integrin, which is expressed on a subset of circulating white blood cells, to mediate the inflammatory process in patients with CD and UC.
Takeda’s BLA submission is supported by four Phase III clinical studies—GEMINI I, II and III, and GEMINI LTS (Long-Term Safety)—which comprise the GEMINI StudiesTM, a clinical program designed to investigate the efficacy and safety of vedolizumab in clinical response and remission in patients with moderate to severe CD and UC. Patients enrolled in the studies failed at least one conventional therapy for inflammatory bowel disease, including corticosteroids, immunomodulators and/or a tumor necrosis factor–alpha antagonist. The results of the Phase III studies of vedolizumab in patients with CD and UC were published recently in the New England Journal of Medicine (Sandborn WJ et al. N Engl J Med2013;369:711-721 and Feagan BG et al. N Engl J Med 2013;369:699-710, respectively).
According to Takeda, vedolizumab has been studied in 2,700 patients in nearly 40 countries, making it the largest Phase III clinical trial program to date to simultaneously evaluate CD and UC. GEMINI LTS is an ongoing, open-label, long-term safety study of vedolizumab and is designed to collect data on the occurrence of important clinical safety events resulting from the administration of vedolizumab.
—Based on a press release from Takeda Pharmaceutical Company Ltd.
Clinical Trial - PUBMED.gov
N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.
http://www.ncbi.nlm.nih.gov/pubmed/?term=23964932Vedolizumab as induction and maintenance therapy for ulcerative colitis.
Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group.
Source
Robarts Clinical Trials, Robarts Research Institute, and Department of Medicine, University of Western Ontario, London, Canada. bfeagan@robarts.ca
Abstract
BACKGROUND:
Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.
METHODS:
We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
RESULTS:
Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0 .001="" 41.8="" 44.8="" 4="" 52="" 8="" and="" at="" ayo="" clinic="" clinical="" continued="" every="" in="" no="" of="" patients="" receive="" remission="" score="" subscore="" to="" vedolizumab="" week="" weeks="" were="" who="">1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0 .001="" 17.9="" 29.1="" 40.4="" 4="" adverse="" and="" ci="" events="" every="" for="" frequency="" groups.="" in="" of="" p="" percentage="" placebo="" points="" similar="" the="" to="" vedolizumab="" vs.="" was="" weeks="">
CONCLUSIONS:
Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
Comment in
- Inhibition of leukocyte trafficking in inflammatory bowel disease. [N Engl J Med. 2013]
- PMID:
- 23964932
- [PubMed - indexed for MEDLINE]