The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) were both prompted to investigate reports of amputation risk from clinical trial data involving canagliflozin, the active ingredient in the type 2 diabetes drugs Invokana and Invokamet. After the EMA’s review, the European agency opted to place increased amputation risk warnings on all drugs in the SGLT2 inhibitors class. The FDA, however, opted to put its strongest warning – a black box warning – only on the safety labels of Invokana and Invokamet.
According to Seeking Alpha, there is no evidence that other drugs in the SGLT2 class have the same risk. “An Advera Health analysis has found no cases of amputation with most of the rest of these products and only a couple with Eli Lilly and Boehringer Ingelheim’s Jardiance,” the analyst publication reported.
The news is yet another nail in the coffin for Johnson & Johnson and Janssen Pharmaceuticals’ Invokana and Invokamet. SGLT2 inhibitors have already been struck with new or strengthened warnings, but Invokana and Invokamet have been hit the worst.
In May 2015, two years after Invokana hit the market, the FDA issued a Drug Safety Communication warning that all SGLT2 inhibitors had been linked to ketoacidosis, a serious condition in which too much acid builds up in the blood. At the same time, the FDA also warned that the drugs had been linked to serious urinary tract infections, which in some cases resulted in a serious blood infection called urosepsis, or a kidney infection called pyelonephritis.
Four months later, the FDA strengthened warnings on Invokana and Invokamet regarding an increased risk of bone fractures as well as decreases of bone mineral density. In June 2016, the FDA announced it was strengthening existing warnings on four SGLT2 inhibitors – Invokana, Invokamet, Farxiga and Xigduo – regarding acute kidney injury.
Analysts say the latest warning on Invokana and Invokamet will likely hurt sales of the drugs.