|AdverseEvents VP Keith Hoffman|
Drugmakers are hot to trot after diabetes meds, and for good reason--the disease population is large, and growing. But the drugs have raised a few eyebrows lately, with regulators taking aim at safety issues tied to SGLT2 and DPP-4 drugs in particular. And SGLT2 and DPP-4 meds are not the only offenders, as side effect reports continue to mount for GLP-1 drugs.
Healthcare informatics firm AdverseEvents looked at post-marketing reports and found heart safety flags for DPP-4 drugs. Takeda's Nesina turned up 5 cases of heart failure and AstraZeneca's ($AZN) Onglyza, a DPP-4 med scrutinized earlier this year for its cardiovascular safety, presented 19 cases, the firm found. Of the SGLT2 inhibitors, AstraZeneca's Farxiga turned up 6 cases of heart failure. GLP-1 drugs showed hardly any heart safety issues in AdverseEvents' analysis.
And while pancreatic cancer and pancreatitis "is not a new worry" when it comes to diabetes meds, the safety reports highlighted by the company give more weight to the issue, Keith Hoffman, vice president of scientific affairs at AdverseEvents, told FiercePharma. The firm's analysis highlighted 1,900 cases of pancreatitis associated with AstraZeneca's Byetta GLP-1 injection, and another 1,284 in patients taking Novo Nordisk's ($NVO) Victoza. Meanwhile, Merck's ($MRK) DPP-4 med Januvia was associated with 1,296 cases of pancreatitis.
Perhaps more worrisome were the reports of pancreatic cancer in patients using these meds. More than 750 Byetta patients turned up with pancreatic cancer, while 335 Victoza patients developed the disease. For the DPP-4 class, there were 696 cases of pancreatic cancer for Januvia and 167 cases for Merck's Janumet.
Novo is standing by Victoza, though, telling FiercePharma in an email that it "remains confident" in its drug's positive risk-benefit profile when it comes to pancreatic safety. "With more than 2.9 million years of patient use worldwide, Victoza has a strong body of evidence to support its safety and efficacy based on both clinical trial and real-world practice data," said Novo's vice president of media relations Katrine Sperling.
The real surprise in AdverseEvents' analysis was reports of ketoacidosis tied to SGLT2 inhibitors, Hoffman said. The FDA last month flagged the SGLT2 class for reports of ketoacidosis, a serious condition in diabetics that can result in emergency room visits. AdverseEvents was drafting its report of diabetes meds when the agency issued its warning, signaling a need for increased vigilance, Hoffman said. Patients on Johnson & Johnson's ($JNJ) Invokana turned up with 23 cases of ketoacidosis, and Farxiga was tied to 16 cases.
"There's a lot of hope around the SGLT2s. So far they look pretty good," Hoffman said. "But ketoacidosis is a major concern that can lead to other complications. So that will have to be addressed with new compounds moving forward."
Still, J&J is not buying the numbers. "We at Janssen take seriously our responsibility to the healthcare professionals and patients who use our medicines," the company told FiercePharma in an email. "In our Phase 3 studies and other controlled studies conducted since then, including more than 17,500 people taking Invokana, the overall incidence of serious adverse event cases of diabetic ketoacidosis (DKA) was less than 0.1 percent."
Newcomers to the diabetes playing field also turned up some troubling safety issues. GlaxoSmithKline's ($GSK) GLP-1 med Tanzeum, which was approved last April, showed 32 cases of "device use error." The cases comprise 10% of all reports for the med. "It certainly pops out," Hoffman said. "If 10% of all the reports that are coming in have this for the drug, there's still something that needs to be addressed there."
But GSK disagrees with AdverseEvents' analysis of Tanzeum. "The number of 'device use' errors quoted in this article does not recognize the fact that this represents less than 0.1% of all the Tanzeum pens injectors dispensed to date in the U.S. We therefore disagree with Mr. Hoffman's conclusion," the company told FiercePharma in an email.
- here's a link to the report (reg. req.)
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Editor's Note: This story was updated with a statement from Johnson & Johnson, GlaxoSmithKline and Novo Nordisk.