The pill, potentially the second to reach the market in a new class of diabetes drugs, has cardiovascular benefit including lower blood pressure and weight loss. Food and Drug Administration staff members were wary that the heart benefits were enough to balance an increased risk of bladder cancer and indications of liver damage, according to a report posted today ahead of a Dec. 12 meeting of advisers to the agency.
The FDA rejected dapagliflozin in January 2012 after a previous advisory panel raised concern about the potential association with cancer. Today’s report cited trials showing increased liver enzymes that indicate damage to the organ of those who took the diabetes pill and an increased potential for heart attack and stroke soon after starting treatment, though FDA staff said there is a long-term cardiovascular benefit.
“As a result of these updated analyses the agency could not conclude with any level of confidence that the purported CV-benefit associated with dapagliflozin use outweighed the observed imbalance in specific malignancies or potential liver toxicity risks,” Jean-Marc Guettier, director of the FDA’s endocrinology product division, wrote in today’s report.
The FDA is scheduled to decide whether to approve the diabetes treatment by Jan. 11. The agency approved Johnson & Johnson (JNJ)’s Invokana in March for Type 2 diabetes that was the first in a class of therapies like dapagliflozin called SGLT2s, which expel sugar in the urine after the kidneys filter it from the blood. New Brunswick, New Jersey-based J&J must study the effects of the pill on the heart while its on the market.
Bristol-Myers, based in New York, and London-based AstraZeneca have proposed post-market surveillance in an ongoing cardiovascular study for the drug they are trying to get approved. Out of 6,045 patients in clinical trials for the drug, 10 were diagnosed with bladder cancer compared to one out of 3,512 patients who took a placebo or older treatments. The companies said studies in rodents and dogs didn’t show evidence of tumors.
An FDA reviewer determined an increased incidence of breast cancer in women who took dapagliflozin in clinical trials was not related to the drug.
Bristol-Myers and AstraZeneca need new drug sales to make up for losses from bestsellers that are losing patent protection. The patent on Bristol-Myers’s Plavix expired last year, taking the blood thinner from a $7 billion drug in 2011 to an estimated $211 million this year. AstraZeneca will have lost patent protection on Nexium and Seroquel by 2014.
Diabetes is the seventh-leading cause of death in the U.S., according to the Centers for Disease Control and Prevention. The disease, defined by high levels of sugar in the blood, affected almost 26 million people in the U.S. in 2010, or about 8.3 percent of the population, the Atlanta-based CDC said.
Dapagliflozin, called Forxiga in Europe where it was approved last year, may generate $141 million in sales for Bristol-Myers next year rising to $1 billion in 2020, according to analysts’ estimates compiled by Bloomberg.
Boehringer Ingelheim, based in Ingelheim, Germany, and Eli Lilly & Co. (LLY), based in Indianapolis, submitted an application for FDA approval of their SGLT2 inhibitor empagliflozin, the companies said in a March 25 statement. Astellas Pharma Inc. (4503) is also working on an SGLT2 inhibitor known as ipragliflozin.
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