FDA Rejects Farxiga/Ongyza Combination Drug, Calls For More Clinical Trials

AstraZeneca says federal regulators have rejected an application for approval of a new diabetes drug that combines the active ingredients in Farxiga and Onglyza, indicating that they have been required to conduct more clinical trials to establish the combo treatment is safe and effective. 

The U.K. drug manufacturer confirmed on Friday that the FDA sent a complete response letter (CRL), rejecting approval of a drug that combines Onglyza (saxagliptin) and Farxiga (dapagliflozin). While the letter has not been made public and AstraZeneca’s press release did not indicate why the agency rejected the new drug, the company said reviewers called for more clinical data.

“This includes clinical trial data from ongoing or completed studies and may require information from new studies,” the press release states. “AstraZeneca will work closely with the FDA to determine the appropriate next steps for the NDA (New Drug Application) and remains committed to the development of the saxagliptin/dapagliflozin fixed-dose combination.”

Farxiga is part of a new generation of diabetes drugs known as sodium glucose cotransporter-2 (SGLT-2) inhibitors. Introduced in 2014, it was the second of this class of drugs; the first of which was Invokana. Other drugs in the same class include Invokamet, Jardiance, Xigduo XR and Glyxambi.

Over the past year, federal regulators have issued several warnings about a potential risks associated side effects of Invokana, Farxiga and other SGLT2 inhibitors, including a risk of diabetic ketoacidosis (DKA), which involves a dangerous build up of acid in the blood

Some researchers have also expressed concerns that the way the medications work by impacting the normal function of the kidneys may be causing a number of reports involving kidney problems on Farxiga and Invokana.

On May 15, the FDA announced an investigation into the mounting number of reports involving diabetic ketoacidosis, ketosis or acidosis among users of Farxiga and other SGLT2 inhibitors, after at least 20 cases of were identified since the new class of diabetes treatments hit the market.

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, 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.

In April, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-1 to recommend stronger warnings about the potential risk of heart failure from Onglyza side effects, after a review of data from clinical trials suggested that users may face a higher than expected risk of hospitalization for heart problems and all-cause mortality.

Onglyza is a DPP-4 inhibitor, 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.

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.

AxtraZeneca predicts that a combination of the two drugs could bring in $3 billion in annual sales. The proposal for a combination therapy comes as many diabetes patients are considering potential Farxiga lawsuits and Onglyza lawsuits against AstraZeneca, over failure to adequately warn about health risks associated with the individual medications.