An FDA panel voted 10-2 that the investigational diabetes drug saxagliptin (Onglyza) does not put Type 2 diabetes patients at an increased risk for cardiovascular events, but wants drugmaker Bristol-Myers Squibb to
An FDA panel voted 10-2 that the investigational diabetes drug saxagliptin (Onglyza) does not put Type 2 diabetes patients at an increased risk for cardiovascular events, but wants drugmaker Bristol-Myers Squibb to conduct long-term postmarketing studies to test the drug in older and sicker patients.
Saxagliptin is the first antidiabetic agent to come under FDA review since the agency adopted stricter standards in 2008 that ask companies to prove their therapy won’t raise the risk of cardiovascular events.
Although the Endocrinologic and Metabolic Drugs Advisory Committee didn’t vote to recommend the FDA approve the drug, the committee’s thumbs-up for safety effectively amounts to an approval recommendation.
When the FDA decides to approve the drug, saxagliptin would become only the second gliptin-class diabetes drug on the market, joining Merck’s sitagliptin (Januvia). The FDA does not have to follow the advice of its advisory panels, but usually does.
The FDA’s new safety standards were issued following controversy over rosiglitazone (Avandia), which was shown to increase cardiovascular event risks.
The saxagliptin trials had already wrapped before the agency released its new recommendations, so Bristol-Meyers Squibb had to determine the cardiovascular risks post-hoc.
According to an FDA review of eight of the company’s randomized, double-blind, controlled trials, both the saxagliptin and the comparator groups saw similarly low rates of cardiac disorders, nervous system disorders, and sudden cardiac death, and there were no statistically significant differences in adverse event rates between the arms of the trial.
There were 11 cardiovascular events in the 24-week, double-blind, short-term study periods and a total of 40 cardiovascular events in a median of 62 weeks exposure. Data culled from those trials showed 0.7% of patients taking saxagliptin experienced a cardiac event during the study, compared with 1.4% of patients in the comparator groups, said FDA analyst Naomi Lowy, M.D. “I think these results do rule out significant harm,” said Michael Proschan, Ph.D., a CDC biostatistician.
“If there is any harm at all, it would have to be very small,” he said.
Although the safety data was positive, the advisory panel voted unanimously that the company should not be exempt from monitoring the drug’s safety in postmarketing trials, which will likely evaluate saxagliptin’s cardiovascular effects in an older and sicker population.
The two “No” votes on the panel came from John Teerlink, M.D., a cardiologist and director of the Heart Failure Clinic at the San Francisco Veterans Medical Center, and Kathleen Wyne, M.D., Ph.D., an endocrinologist at the Methodist Hospital Research Institute in Houston.
Drs. Wyne and Teerlink said the total number of events were too small to determine the drug would be safe in a real-world setting. They were also concerned that the patients included in the company’s trials were younger and more recently diagnosed — and therefore healthier — than would be expected in a clinical setting.
The average age in the trials was 55, and just 10% of the patients had been diagnosed with diabetes 10 years or more before enrollment. Most had been diagnosed just five years previously.
“Not seeing an increase in events in a young, early diagnosis group can be reassuring,” said Dr. Wyne. “But because you don’t have a high-risk group, you don’t know if it truly makes a difference.
Manufacturers of other diabetes drugs awaiting FDA approval will also have to strive to meet the new guidelines. An FDA official said she wasn’t sure how many drugs fall into that category but it does include Novo Nordisk’s liraglutide, which the same advisory panel will consider tomorrow.