AstraZeneca and Takeda DPP-4 inhibitors get another warning added to their labels

There is more bad news for DPP-4 inhibitor diabetes drugs saxagliptin and alogliptin from AstraZeneca ($AZN) and Takeda. The FDA has tightened its regulatory grip on the Type 2 diabetes meds, insisting their labels now include warnings of increased risks of heart failure.

In a notice on Tuesday, the FDA called out by name AstraZeneca's Onglyza and combo drug Kombiglyze XR as well as Takeda's Nesina and combos Kazano and Oseni. AstraZeneca's drug are based on saxagliptin and Takeda's on alogliptin.

It comes at a particularly tough time for AstraZeneca and Takeda which have banked on sales from the diabetes drugs to help turn around flagging fortunes. It also may be a boost the fortunes of competitor drugs like Merck's ($MRK) Januvia, which also is a DPP-4 drug but will not carry the warning. Januvia has a different active ingredient, sitagliptin, and data from a trial released last year showed no increased risk of heart disease. Better yet, data last year on Jardiance, a different class of diabetes drug called a SGLT2 from Eli Lilly & Co. ($LLY) and Boehringer Ingelheim, showed that it actually lowers the risk of heart attack, stroke and death from cardiovascular causes.

The new label warning comes a year after an FDA advisory panel overwhelmingly recommended the warning during a review of Onglyza. The FDA says it reached its decision after reviewing data from two large clinical trials of the drugs in patients with heart disease. What they found was that 3.5% of patients taking saxagliptin were hospitalized with heart failure compared to 2.8% of patients on a placebo. For alogliptin, the rate was 3.9% vs. 3.3%, the FDA reported.

It is the second time in less than a year that the FDA has added a warning to the labels of DPP-4 inhibitors. In August it said the labels would have to add that the class of meds might cause "severe and disabling" joint pain. Merck's Januvia was included in that warning.

AstraZeneca CEO Pascal Soriot

The concerns already appear to be whittling down sales of Onglyza in the U.S. Globally last year, revenues for the drug were flat at $786 million but were down 13% in the U.S. to $420 million. When AstraZeneca was fighting off a takeover from Pfizer ($PFE) in 2014, CEO Pascal Soriot promised to deliver annual revenue above $45 billion by 2023, with $8 billion of that sum coming from its diabetes portfolio.

That pledge also got gut kicked last fall when the FDA put off approval of an AstraZeneca new SGLT2/DPP-4 combo, a mix of Onglyza and Farxiga, asking for more data. While it was unclear whether the delay was tied to concern over heart risks, the request may delay approval by more than a year. AstraZeneca had hoped to generate $3 billion in peak sales for the drug but now may have to cede much of that to competitors.

- here is the FDA notice

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