(Reuters) – AstraZeneca Plc’s diabetes drug Onglyza may be associated with an increased rate of death, according to a preliminary review of data by the U.S. Food and Drug Administration.
The FDA’s report, posted on the agency’s website on Friday, comes ahead of an April 14 meeting of an FDA advisory panel to discuss the safety of Onglyza and a similar drug from Takeda Pharmaceutical Co called Nesina. Onglyza won U.S. approval in 2009 and Nesina in 2013.
A trial of more than 16,000 patients known as SAVOR previously showed patients taking Onglyza, also known as saxagliptin, had an increased risk of hospitalization due to heart failure.
The agency’s 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 reveal a higher death risk, but a more detailed analysis examining only patients who took the drug suggests “a significantly increased risk of all-cause mortality,” the review found.
The FDA said the causes of death were often “multifactorial” and some patients may have had several serious medical conditions prior to death.
Still, the FDA said it “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.”
A similar large study of Takeda’s Nesina (alogliptin) from the same class of drugs, called DPP-4 inhibitors, did not raise similar concerns, FDA documents found.
In that study, called EXAMINE, the time to first occurrence of cardiac death, heart attack or non-fatal stroke seen in those taking Nesina was nearly identical to those taking a placebo, and there was no statistically significant difference in the rate of hospitalization for heart failure observed with Nesina.
Wall Street and the medical community are awaiting heart safety results from a large trial of Merck’s $4 billion a year Januvia, the market leading DPP-4 inhibitor, to help determine if increased risk is related to the drug class or limited to individual drugs. Those results are expected in June.
Leerink analyst Seamus Fernandez said the FDA’s concerns over all-cause mortality were unexpected and could lead to a cut of up to 50 percent in his $1.8 billion Onglyza peak annual sales estimate, if Januvia does not show similar problems.
In December 2008, the FDA issued guidance requiring drug companies to conduct studies to show that new diabetes drugs do not increase cardiovascular risk. The guidance was developed amid growing concern about the safety of many diabetes drugs.
AstraZeneca said the SAVOR study met the objective of showing that patients taking Onglyza were not at greater risk as measured by a composite benchmark comprising cardiovascular death, non-fatal heart attack and non-fatal ischemic stroke.
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AstraZeneca, whose shares slipped 0.2 percent after paring larger declines, said it would “work closely with the FDA to support further review of the data.” Merck shares were off 0.6 percent. (Additional reporting by Ben Hirschler in London and Bill Berkrot in New York; Editing by Susan Heavey and Dan Grebler)