Bristol-Myers Squibb Co. and AstraZeneca Plc. said patients taking their experimental diabetes pill, shown effective in a two-year study, had more breast and bladder cancers than those on a standard drug.
In all the clinical programs, nine breast cancers and nine bladder cancers were seen among 5,478 patients taking the drug, dapagliflozin, compared with one breast and one bladder cancer among the 3,156 in control groups, Bristol-Myers and AstraZeneca said in a statement today. There was no imbalance in overall cancer risk, the companies said.
The dapagliflozin cancer findings will be a topic at a U.S. Food and Drug Administration advisory panel on July 19, said Mark Schoenebaum, an analyst for ISI Group. The treatment is facing increased scrutiny from regulators and doctors after two rivals were tied to malignancy and heart risks. Data presented today at the American Diabetes Association meeting in San Diego has been shared with the FDA, the companies said.
“No doubt they’ll bring this up at the advisory committee,” Schoenebaum said in an interview today. “But I’d be very surprised if this blocked approval.”
Patients probably already had the cancer when they enrolled in the trial, Schoenebaum said. The timing of the cases made it seem unlikely that dapagliflozin caused the cancers, although it may have accelerated them, he said.
What is likelier is that the agency will require a post-marketing study on cancer risks, he said. At the very worst, there may be a black box warning on the drug, Schoenebaum said.
“We look at this very seriously,” said Elisabeth Svanberg, the vice president of development for New York-based Bristol-Myers, in an interview today. In preclinical studies in rats and mice, where the animals were given up to 100 times the human dose, dapagliflozin didn’t increase cancer risks, Svanberg said.
“It’s probably a numerical imbalance,” she said. “Those occur in clinical trials.”
Results from a two-year study released yesterday reported that dapagliflozin in combination with metformin, a standard treatment, was safe and effective. The study, funded by Bristol-Myers and London-based AstraZeneca, showed that patients getting dapagliflozin lowered their blood sugar more than patients on metformin and another generic diabetes drug, glipizide.
An estimated 25.8 million Americans have diabetes, most of the Type 2 variety linked to weight gain and a lack of exercise, according to the U.S. National Institutes of Health.
Avandia, Actos Risks
In May, U.S. regulators restricted use of London-based GlaxoSmithKline Plc’s Avandia, ordering the drug to be pulled from pharmacy shelves and made available only through a special program. Sales of Avandia fell to $680 million last year from $1.8 billion in 2007 after a study that year showed a 43 percent increased risk of heart attacks among patients taking the medicine.
On June 15, a five-year analysis from a decade-long company-sponsored study of Osaka-based Takeda Pharmaceutical Co.’s Actos showed an increased risk of bladder cancer. Actos is the world’s biggest-selling diabetes drug. The FDA had required the study under new guidelines for diabetes drug approvals.
Dapagliflozin works differently than Actos and Avandia. While those drugs adjust the hormone that regulates blood sugar, the new pill helps patients excrete sugar through their urine.
The new mechanism would make dapagliflozin the first entry in a class called SGLT-2 inhibitors that work by allowing patients to excrete their excess blood sugar in their urine. Johnson & Johnson, Eli Lilly & Co., Boehringer Ingelheim GmbH, and Astellas Pharma Inc. are among the companies pursuing similar drugs.
The breast and bladder don’t express SGLT-2, Bristol-Myers and AstraZeneca said in the statement.
Patients on dapagliflozin were more likely to have urinary tract and genital infections than those taking metformin alone, according to the two-year results released yesterday.