AstraZeneca's diabetes drug Onglyza is associated with higher risk of premature death and heart failure, a preliminary report released Friday by the U.S. Food and Drug Administration said.
The analysis, which will be presented to an FDA advisory committee meeting on April 14, raises new concerns over a class of diabetes medications that have been linked to serious side effects and patient harm. Onglyza, as well as Takeda Pharmaceuticals diabetes drug Nesina, fall within a class of drugs called DPP-4 inhibitors, which are used to control blood glucose levels in type 2 diabetes patients.
A post-marketing study of Onglyza, which involved more than 16,000 patients, showed the drug increased hospitalizations for heart failure by 27% and increased all-cause mortality, though the agency noted deaths in those patients often involved multiple factors, according to briefing documents posted to the agency's website on Friday.
The report stated “…sensitivity analyses conducted by the FDA, which included only death as occurring while patients were exposed to treatment, suggested significant or near significant increases in all cause mortality.” Onglyza received FDA approval in 2009 and reportedly generated more than $800 million in sales in 2014.
Similar results were not found in the Nesina study. Patients taking the drug did not have a significant increase in the number of hospitalizations compared to the control group.
Safety concerns regarding DPP-4 inhibitors had been raised for years, prompting the FDA in 2008 to issue guidance that required manufacturers of those types of drugs to provide evidence that their products did not carry increased cardiovascular risk.
While results of the Nesina trial fell within acceptable parameters for risk, the all-cause mortality risk found in the Onglyza trial came as a “surprise,” according to Seamus Fernandez, an analyst at the investment research firm Leerink Partner LLC.
Tuesday's advisory committee's recommendations on what, if any, action the FDA should take regarding Onglyza could have large implications for other makers of DPP-4 inhibitors. Merck has yet to release its post-market study of Januvia, which got approval in 2006 and reported sales totaling $3.9 billion in 2014, according to the company's year-end financial statement.
If the Merck trial shows Januvia does not have the same type of problems raised in the Onglyza study, the result could be a 50% cut in sales for AstraZenenca drug, according to Fernandez.
In a research note to stockholders, Fernandez predicted it was unlikely the FDA advisory panel would recommend pulling Onglyza from the market. A more likely outcome was restricting distribution or requiring a laeling change that would add new safety information, he said.
Shares of AstraZeneca were down by .3% selling at $69.92 a share on Friday afternoon.