June 25, 2011 / 6:36 PM / in 7 years

Bristol diabetes pill tied to certain cancers

SAN DIEGO (Reuters) - A new type of diabetes pill being developed by Bristol-Myers Squibb and AstraZeneca was effective in a two-year study but more bladder and breast cancers have been found in patients treated with the drug.

In all studies so far completed, 1.4 percent of patients treated with dapagliflozin developed some type of cancer, compared with 1.3 percent of control group patients, said Elisabeth Bjork, vice president of development for dapagliflozin at AstraZeneca.

Nine bladder cancers have been observed in 5,478 patients treated with the experimental drug, compared with one bladder cancer seen in the 3,156 patients in control groups.

Six of the 10 had blood in the urine, known as hematuria, when they entered trials and five were diagnosed within a year after their study started.

The companies also said nine cases of breast cancer have occurred in 2,223 women on dapagliflozin and one has been observed out of 1,053 women in control groups. All were diagnosed within a year after studies started.

ISI Group analyst Mark Schoenebaum said the timing of diagnosis within a year of therapy initiation and hematuria at baseline could be mitigating factors but the cancer findings are sure to be discussed by regulators.

He estimated a rejection of the drug would cut Bristol-Myers’ 2015 earnings by between 3 percent and 6 percent.

Analysts, on average, have forecast the U.S. company’s annual dapagliflozin sales at $631 million by 2015, according to Thomson Pharma.

Bjork said studies of dapagliflozin in animals found no carcinogenic signals.

“Importantly, overall cancers are not imbalanced,” she said.

Bristol and AstraZeneca filed earlier this year for U.S. and European regulatory approval of dapagliflozin. An advisory committee to the U.S. Food and Drug Administration is set to review the application on July 19.


It is potentially the first in a new class of diabetes drugs designed to block glucose from being absorbed into the bloodstream through the kidneys, allowing more sugar to be excreted with urine.

People with diabetes have inadequate blood sugar control, which can lead to serious complications like heart disease and stroke, as well as damage to the kidneys or nerves, and to blindness.

Dapagliflozin leads to more sugar in the urine, which may serve as a nutrient for bacteria and pathogens that can cause infections, said Elisabeth Svanberg, vice president of development for dapagliflozin at Bristol-Myers.

In a two-year trial, urinary tract infections were seen in 8 percent of Type 2 diabetes patients treated with a placebo and the generic drug metformin, 8 percent of patients on a 2.5 mg dose of dapagliflozin plus metformin, 8.8 percent of patients on a 5 mg dose and 13.3 percent of patients receiving dapagliflozin 10 mg.

Genital infections were seen in 5.1 percent of patients receiving placebo plus metformin, compared to 11.7 percent for patients on the lowest dose of dapagliflozin plus metformin, 14.6 percent of patients on the 5 mg dose and 12.6 percent of patients on the 10 mg dose.

Other side effects included back pain, influenza, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, renal impairment or failure and events of hypoglycemia, according to data presented at the annual meeting of the American Diabetes Association.

In addition, one patient treated with the 5 mg dapagliflozin dose was diagnosed with transitional cell bladder cancer. One woman treated with 10 mg dapagliflozin was diagnosed with breast cancer.

Events of renal impairment or failure were reported in 1.5 percent of patients treated with placebo plus metformin, compared to 4.4 percent of patients on the lowest dose of dapagliflozin.

The 546-patient trial showed that the experimental drug resulted in greater and sustained improvements in glycemic control and sustained reductions in body weight compared to placebo, according to Cliff Bailey, head of diabetes research at Aston University, in Birmingham, England, and the study’s lead investigator.

Editing by Sandra Maler and Bill Trott

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