Onglyza Heart Failure Warnings Should Be Added, FDA Advisors Say

The diabetes drug Onglyza should carry additional label warnings about the risks of heart failure and death, according to recommendations issued by a panel of expert advisors to the FDA. 

In a 14-1 vote, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended new label warnings for Onglyza this week, based on a review of data from clinical trials that suggested users may face a higher than expected risk of hospitalization for heart failure and all-cause mortality. The FDA must now decide whether to follow the panel’s recommendations.

Onglyza (saxagliptin) was developed jointly by AstraZeneca and Bristol-Myers Squibb, but is now owned wholly by AstraZeneca. It was approved by the FDA in July 2009 for treatment of type 2 diabetes, and the medication is part of a class of drugs known as incretin mimetics, which also includes Januvia, Janumet, Byetta, Victoza and other widely used medications. However, only drugs with the active ingredient saxagliptin are being reviewed.

At issue is data collected from a clinical trial known as SAVOR, which involved 16,492 subjects with type 2 diabetes, some of whom were given Onglyza, and some of whom were given a placebo.

In a press release issued by AstraZeneca on April 14, the company said it will conduct its own interview to better understand the SAVOR results, which FDA reviewers say revealed there may be a 27% increased risk of heart failure hospitalization linked to side effects of Onglyza. They also found both increases in cardiovascular death and death from all causes.

The FDA’s advisory committee had several possible options, including new label warnings, limiting Onglyza’s availability, or recommending an Onglyza recall. In the end, only one committee member voted for a recall. The other 14 called for new label warnings.

While the panel’s recommendations are not binding on the FDA, the agency usually weighs advisory committee recommendations heavily when making a final ruling.

Onglyza Pancreatic Cancer Concerns

Onglyza is a DPP-4 inhibitor, which is part of a class of drugs known as incretin mimetics, which works by mimicking the incretin hormones the body usually produces to naturally stimulate the release of insulin in response to a meal. The diabetes drug brought in more than $700 million in sales in 2012. Other DPP-4 inhibitors include Nesina and Januvia.

Some of the panelists suggested that the health risks may be a class effect, meaning the labels for Januvia and Nesina would need to be updated as well.

The FDA launched an investigation into the potential heart risks with Onglyza last year, following the publication of the SAVOR study by the New England Journal of Medicine in 2013.

In addition to the potential risk of heart failure, studies have suggested that users may face a risk of pancreatic cancer from Onglyza and other incretin mimetic diabetes drugs.

A number of Byetta lawsuits, Januvia Lawsuits, Janumet lawsuits and Victoza lawsuits are currently pending in courts throughout the country involving similar incretin mimetic diabetes drugs, alleging that the makers of those medications failed to adequately warn about the risk that users may develop pancreatic cancer.

The incretin mimetic litigation pending throughout the federal court system has been consolidated as part of an MDL, or Multidistrict Litigation, which is centralized before U.S. District Judge Anthony J. Battalglia in the Southern District of California to reduce duplicative discover, avoid conflicting pretrial rulings from different judges and to serve the convenience of the parties, witnesses and the courts.