Increased Rate of Death. After a preliminary review of data, the Food and Drug Administration (FDA) reports that AstraZeneca’s diabetes drug Onglyza (saxagliptin) may be associated with an increased rate of death.
The FDA’s report was posted on the agency’s website on Friday, a few days ahead of an April 14 FDA advisory panel meeting to discuss the safety of Onglyza and Takeda Pharmaceutical’s similar drug, Nesina, Reuters reports. Onglyza won FDA approval in 2009, Nesina in 2013.
The SAVOR trial of more than 16,000 patients showed patients taking Onglyza had an increased risk of hospitalization due to heart failure.
SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) is the largest cardiovascular outcomes trial to study a diverse population of type 2 diabetes patients at high risk for cardiovascular events.
The FDA analysis found the heart failure risk to be valid, and also identified a possible increased risk of death from all causes.
The overall trial results did not indicate a higher death risk, but an analysis looking at only patients who took the drug suggests “a significantly increased risk of all-cause mortality,” according to Reuters.
The causes of death were often “multifactorial,” the FDA said
The causes of death were often “multifactorial,” the FDA said, meaning that some patients may have had several serious medical conditions that contributed to death. But the FDA statement said the agency is “not reassured” by the increased risk, “and we do not necessarily view this pattern of variable causes as evidence the mortality signal is due to chance.”
In December 2008, amid growing concern about the safety of many diabetes drugs, the FDA issued guidance requiring drug makers to conduct studies to show that new diabetes drugs do not increase cardiovascular risk. The FDA recommended that manufacturers of new diabetes drugs “carefully design and evaluate their clinical trials for cardiovascular safety.”
In a similar large study of Nesina (alogliptin), a DPP-4 inhibitor (the same class as Onglyza) did not raise similar concerns, according to FDA documents. The EXAMINE study showed that the time to occurrence of cardiac death, heart attack or non-fatal stroke in those taking Nesina was nearly identical to those taking a placebo, Reuters reports.
The study showed no statistically significant difference in the rate of hospitalization
The study showed no statistically significant difference in the rate of hospitalization for heart failure associated with Nesina.
The leading drug in the class, Merck’s drug Januvia (sitagliptin), is subject of a large trial to determine if the risks are related to the whole drug class or limited to individual DPP-4 inhibitors. The results of that trial are expected in June 2015.
On July 31, 2009, the FDA approved Onglyza, a once-a-day tablet to treat Type 2 diabetes in adults. The FDA’s news release said Onglyza “is intended to be used with diet and exercise to control high blood sugar levels.”
AstraZeneca said the SAVOR study showed patients taking Onglyza were not at greater risk measured by a composite benchmark including cardiovascular death, non-fatal heart attack and non-fatal ischemic stroke, according to Reuters.