In the past five years, the FDA has identified a dozen cases of a rare flesh-eating infection in patients taking SGLT2 diabetes drugs. The condition—called Fournier’s gangrene, or necrotizing fasciitis of the perineum—can be caused by diabetes itself, but the agency is requiring SGLT2 drugmakers to add a warning about the risk to their labels.
The warning will hit 13 products from Eli Lilly and Boehringer Ingelheim; Johnson & Johnson; AstraZeneca; Merck and Pfizer. All of the drugs have been linked to cases of Fournier’s except for Merck’s Steglatro (ertugliflozin), which was approved late last year. But that product will need to carry the warning anyway, the FDA said in its announcement.
The new warning is not likely to slow down SGLT2 sales growth, which has been fueled in part by heart-helping data from Lilly and Boehringer Ingelheim's Jardiance, the first diabetes drug to show it could cut the risk of CV events and death. Nearly 2 million patients filled prescriptions for SGLT2 inhibitors in 2017, according to the FDA, and the drugs are expected to pull in $7 billion in combined sales by 2020, Bloomberg estimated.
The FDA reported Thursday that seven cases of the Fournier's gangrene occurred in men and the rest in women, and on average the condition emerged about nine months after they started taking an SGLT2 inhibitor. All of the patients were hospitalized and one died, the agency said.
To determine whether the condition was linked to the drugs, the FDA searched its adverse event database going back to 1984. It found just six cases of Fournier’s gangrene, all in men.
“This contrasts with the findings for Fournier’s gangrene with the SGLT2 inhibitors where more cases were reported over a shorter timeframe, and cases involved both males and females,” the document said.
Spokespeople for Merck, Johnson & Johnson’s Janssen unit, BI, Lilly and AstraZeneca said in emailed statements that the companies are discussing the labeling update with the FDA. Janssen makes the Invokana family of SGLT2 inhibitors, while AstraZeneca makes Farxiga and related products. Lilly and BI are teamed up on Jardiance and related products, and a Lilly spokesperson said in an email to FiercePharma that the companies monitor product safety "on an ongoing basis" in both clinical trials and real-world use.
“Although diabetes is a risk factor for Fournier’s gangrene, across more than 35 completed and ongoing Phase 2b/3 trials in over 35,000 patients, no cases of Fournier’s gangrene have been identified with our medicine,” said the AstraZeneca spokeswoman. Merck's spokesperson also said no cases of the disorder cropped up in Steglatro clinical trials.
Meanwhile, clinical trial data continues to show the benefits of SGLT2 drugs as drugmakers in the class duke it out for market share. In June, for example, a head-to-head study of AZ's Farxiga versus Merck’s Januvia, a DPP-4 inhibitor, showed that the SGLT2 drug was more effective at cutting the risk of hospitalization and death from heart attack and stroke. And at the American Diabetes Association’s annual meeting in June, Lilly and Boehringer reported that Jardiance lowered the risk of new or worsening kidney disease compared with placebo.
Meanwhile, all the SGLT2 players have been working to win new indications for their drugs as a way to hone their marketing edge. In July, for instance, the FDA handed J&J a major disappointment, pushing back its verdict on a new indication for Invokana, namely to reduce the risk of cardiovascular events in patients with Type 2 diabetes. The agency asked for additional analyses, putting it behind Lilly and BI, which got the thumbs-up to trumpet a 38% reduction in CV deaths on Jardiance’s label in December.
Nevertheless, J&J was able to celebrate some good news a few days later. The company halted a renal outcomes study early because of Invokana's positive showing. The company plans to present full data from the trial at an upcoming conference, it said, and ultimately, it hopes to market the drug to treat patients with both chronic kidney disease and Type 2 diabetes.
Editor's note: This story has been updated to include input from BI and Lilly.