Showing posts with label new treatment. Show all posts
Showing posts with label new treatment. Show all posts

Friday, December 20, 2013

#Vedolizumab - Favorable Among FDA for Ulcerative #Colitis & #Crohns

Good News!!  The FDA supports the approval of Vedolizumab for the treatment of Crohn's disease and ulcerative colitis.  The treatment looks extremely promising with a safety profile to be recognized.  
Hey, If I would consider the treatment, it has to have minimal/low risks in regard to serious side effects that a lot of biologics have.  Vedolizumab is looking good in the safety department.
The FDA will make the decision to either approve or deny treatment for use among ulcerative colitis (UC) patients by Feb. 18.  The decision for Crohn’s disease (CD) patients will be several months later around June. 




SILVER SPRING, Md. -- Most members of an FDA advisory committee support approval of the investigational biologic agent vedolizumab for Crohn's disease, as well as supporting an additional indication for ulcerative colitis.


In the closest vote of the Gastrointestinal Drugs and Drug Safety and Risk Management joint advisory committee meeting, the members voted 12-9 in favor of recommending approval of the drug for its Crohn's indication as an induction therapy, while the panel voted 20-0, with one abstention, to greenlight the drug as a maintenance therapy for the condition.
"While the data for Crohn's disease don't appear quite as strong, there does appear to be some efficacy and particularly the 10-week data were compelling," noted panelist Linda Feagins, MD, of the University of Texas Southwestern Medical Center in Dallas. She added that "the need for other treatment for Crohn's disease is great and we see that every day treating our patients, and I feel that doing further trials and holding this for patients will increase costs and delay drug availability."
Because the meeting was delayed by 2 hours due to inclement weather, the panel announced early in its Monday session that it would skip a formal vote on the ulcerative colitis indication, citing overwhelming evidence in its favor.
Vedolizumab's manufacturer, Takeda Pharmaceuticals, submitted the drug for approval for the Crohn's disease and ulcerative colitis patient population who had moderate to severely active disease and who were inadequately treated with, did not respond to, or were intolerant of convention therapy or a tumor necrosis factor-alpha antagonist.
Phase III trial data showed the drug was effective in ulcerative colitis patients, but only one of two trials showed drug efficacy at 6 weeks for Crohn's disease. However, data presented during the panel meeting out to 52 weeks of treatment showed significant improvements in remission rates among those who received drug treatment for 4 and 8 weeks.


Another issued raised prior to the panel discussion were concerns over risks for progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal demyelinating condition that can occur in patients receiving natalizumab (Tysabri) and other immunosuppressive medications and who are infected with JC virus.
However, in the only unanimous vote of the session, all 21 panelists voted Yes that Takeda had sufficiently accounted for the risk of PML to support approval; Takeda said that although no cases had occurred during phase III studies, the company would still conduct post-market research and include a warning in its packaging. The panel routinely supported its vote with praise for the risk mitigation strategy and post-market research.
Another vote concerned whether concomitantly administered immunosuppressants should be limited to a specific duration. The panel voted 19-1, with one abstention, against such a limit.
For each condition, the panel voted on whether benefits outweighed risks to support approval of the drug in patients who failed steroid, immunosuppressive, or TNF-alpha antagonists; immunosuppressants or TNF-alpha antagonists; or neither. The vote for ulcerative colitis favored treatment for all conditions, with 14 voting for the first option, seven voting for the second, and none voting for the third. Similarly for Crohn's disease, 14 favored the first option, six favored the second, and one panelist favored neither.
Regarding the vote for the ulcerative colitis indication, committee member Elaine Morrato, DrPH, of the Colorado School of Public Health in Aurora, voted for the least restrictive option, but noted that "the products should be effective, but I worry that a specific requirement for failure of immunosuppressant or anti-TNF would be overly burdensome when you're translating this into clinical practice," adding that she "would rather have those discussions left with the patient and the provider."
Those favoring the middle option preferred a bottom-up approach while waiting for additional data on which patient populations would be best served by the drug with the least risk.
The agency is not required to follow the advice of its advisory committees, though it often does.

Tuesday, October 1, 2013

Vedolizumab, A New Treatment for Ulcerative Colitis & Crohn's Disease Looks Promising - Info & Clinical Trial Included

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.  

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

  2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.

Vedolizumab as induction and maintenance therapy for ulcerative colitis.

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.).
PMID:
 
23964932
 
[PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/?term=23964932