Sign up for our complimentary
weekly e-journal

Main Newsletter
Mastery Series
Therapy Series
 
Bookmark and Share | Print Article | Items for the Week Previous | All Articles This Week | Next
This article originally posted 20 July, 2011 and appeared in  MedicationType 2 DiabetesIssue 583Public HealthSGLT2

Diabetes Drug Dapagliflozin Rejected by FDA Panel

A federal advisory committee voted 9 to 6 on July 19 that a first-of-its-kind diabetes drug should not be approved for use because of safety concerns, including a possible increased risk of breast and bladder cancers....

Advertisement

The advisory committee to the FDA said that while the drug, dapagliflozin, had some attractive features as a treatment for type 2 diabetes, there were too many unanswered questions about safety and in which type of patients it should best be used.

The drug, being developed by Bristol-Myers Squibb and AstraZeneca, could become the first to work to lower blood sugar by causing it to be excreted in the urine. Many other companies are in a heated race to develop similar drugs, which are called SGLT2 inhibitors.

Dr. David M. Capuzzi, a professor at Thomas Jefferson University and a member of the committee, who voted 'no,' stated that, "While I really liked the concept, we just don't have enough right now, in my opinion, to ensure safety and efficacy and how to use it." 

The FDA is not bound to follow the advice of its committees, and it has often said that when a vote is close it pays more attention to the discussion than to the final tally. Still, it would be highly unusual for the agency to immediately approve a drug after a negative vote. The agency is supposed to make a decision by Oct. 28.

Some doctors on the committee said that there was a need for new drugs and that dapagliflozin would be useful in treating type 2 diabetes.

One reason, they said, was that its mechanism of action was different from many other diabetes drugs, which work by affecting the supply or use of insulin. That could make it easier to combine dapagliflozin with other drugs. Also, since so many calories are excreted through the urine, dapagliflozin causes a small weight loss while many other diabetes drugs cause weight gains.

"Finding anti-diabetic agents that are weight-neutral is going to be a huge advance," said Dr. Ellen W. Seely, an endocrinologist at Harvard Medical School and Brigham and Women's Hospital, who voted in favor of approval. "Although there is a scare factor to the word 'cancer'," she said, diabetes "is a devastating disease."

Several committee members said they could have voted either way.

"I changed my mind about four times in the last 10 seconds," said Erica H. Brittain, a statistician at the National Institutes of Health who voted 'no.'

The biggest safety concern was that in clinical trials, patients who got the drug were more likely to develop breast and bladder cancers than those in the control groups.

About 0.4 percent of women taking the drug got breast cancer, compared with 0.1 percent of the women in the control groups. About 0.3 percent of men getting the drug got bladder cancer, compared with about 0.05 percent of men in the control groups.

The numbers were very small, however, making it hard to draw definitive conclusions. Bristol-Myers and AstraZeneca argued that many of the cancers occurred too soon to have been caused by the drugs. Still, some committee members said the imbalance could not be overlooked. "The breast and bladder cancers, I can't dismiss as being irrelevant or minor," said Dr. Doris B. Strader of the University of Vermont.

Another safety concern was that there was one case of liver damage probably caused by the drug. And some committee members said Bristol-Myers and AstraZeneca had not done enough studies of how exactly the drug affected the kidneys. Some also said the clinical trials did not include enough minorities and very old patients, demographics that are prone to diabetes.

The committee members agreed that more study of the possible cancer risks and other safety questions would be needed. Those who voted 'no' mainly believed that the studies needed to be done before approval, even though that might delay approval by years.

Those who voted yes tended to think it would be impossible to do large enough studies to rule out the cancer risk before approval. Rather they said the studies could be done after approval, in part by observing the effects of the drug as it is used.

FDA, July 19, 2011
Advertisement


 

Bookmark and Share | Print | Category | Home

This article originally posted 20 July, 2011 and appeared in  MedicationType 2 DiabetesIssue 583Public HealthSGLT2

Past five issues: Diabetes Clinical Mastery Series Issue 185 | GLP-1 Special Editions April 2014 | Issue 725 | SGLT-2 Inhibitors Special Edition April 2014 | Diabetes Clinical Mastery Series Issue 184 |

2014 Most Popular Articles:

Patient Handout: 7 Tips to Drop Excess Pounds with Diabetes
Posted April 04, 2014
Who Qualifies for Statin Treatment under the New Guidelines?
Posted March 27, 2014
Surprising Trends in the Use of Antidiabetic Drugs
Posted March 27, 2014
Emergency Recall of the OTC Weight-loss Drug Alli
Posted April 10, 2014
STAMPEDE 3 Results: Bariatric Surgery vs. Intensive Medical Therapy
Posted April 10, 2014
Strong Association between Mediterranean Diet and Lower Risk of Diabetes
Posted April 10, 2014
FDA Approves Albiglutide, a Once-Weekly GLP-1 Injectable Diabetes Drug
Posted April 17, 2014
Diabetes Medications Are the Most Expensive
Posted April 10, 2014
Dark Chocolate: Has the Mystery Been Solved?
Posted April 10, 2014
Lifestyle Changes during Prediabetes Can Reduce Mortality
Posted April 10, 2014


Browse by Feature Writer & Article Category.
A. Lee Dellon, MD | Aaron I. Vinik, MD, PhD, FCP, MACP | Beverly Price | Charles W Martin, DD | Derek Lowe, PhD | Dr. Bernstein | Dr. Brian Jakes, Jr. | Dr. Fred Pescatore | Dr. Tom Burke, Ph.D | Eric S. Freedland | Evan D. Rosen | Ginger Kanzer-Lewis | Greg Milliger | Kristina Sandstedt | Laura Plunkett | Leonard Lipson, M.A. | Louis H. Philipson | Maria Emanuel Ryan, DDS, PhD | Marilyn Porter, RD, CDE | Melissa Diane Smith | Michael R. Cohen, RPh, MS, ScD, FASHP | Paul Chous, M.A., OD | Philip A. Wood PhD | R. Keith Campbell, Professor, B.Pharm, MBA, CDE | Sheri R. Colberg PhD | Sherri Shafer | Stanley Schwartz, MD, FACP, FACE | Steve Pohlit | Steven V. Edelman, M.D. | Timothy S. Hollingshead |
Advertisement
Diabetes In Control Advertisers

Cast Your Vote
Are weight loss programs doing a good job incorporating into your diabetes programs?
CME/CE of the Week
NEW! How Do We Optimize with Antiplatelet and Anticoagulant Therapies? 
from the Acute Coronary Education Summit - July 27-28, 2011

Category: Cardiology
Time: 240 minutes



Search Articles On Diabetes In Control