The US Food and Drug Administration (FDA) staff reviewers have raised serious concerns of safety issues associated with AstraZeneca’s diabetes drug Onglyza.
The agency’s concerns come a few days ahead of a committee meeting to discuss the safety of DPP-4 inhibitors. The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee is scheduled to meet on Tuesday, April 14 to review data from a large scale cardiovascular (CV) outcomes trial that assessed if there was an effect on CV risk in patients with type 2 diabetes who were taking AstraZeneca’s Onglyza or Takeda’s Nesina, both of which are DPP-4 inhibitors.
According to the agency’s report, the reviewers did not find an increase in deaths related to Nesina, however the FDA’s review did find that patients taking Onglyza may have had a significantly increased risk of all-cause mortality. The FDA reviewers said that while there was not a statistically significant increase in death rate of patients during clinical trials, when they looked at data on just patients taking Onglyza, the risk appeared evident.
AstraZeneca’s trial, known as SAVOR, evaluated more than 16,000 patients with type 2 diabetes. The study showed that patients taking Onglyza had an increased risk of hospitalization due to heart failure. The FDA’s analysis found the heart failure risk valid and also identified a possible increased risk of death from all causes. The agency said that the causes of death were often “multifactorial” and some patients may have had multiple serious medical conditions in the days and weeks before death. However, the FDA said that it is not reassured by the increased risk and that it does not “necessarily view this pattern of variable causes as evidence the mortality signal is due to chance.”
Onglyza was approved by the agency in 2009, and generated $820 million in sales last year for AstraZeneca.
The advisory panel is also supposed to review Merck’s DPP-4 inhibitor Januvia, which generated $3.93 billion in sales last year. However, while Merck’s trial on Januvia is complete, the results have yet to be released. The company said that it plans to present results of the study at the American Diabetes Association meeting in June.
The committee will comment on their level of concern regarding the data and will assess whether there is a class effect to be considered. The committee will come to a conclusion, and make a recommendation to the FDA, however the agency is not required to follow the recommendation.
Source: US Food and Drug Administration
Last updated: 4/10/15; 1:30pm EST