Two years after AstraZeneca ($AZN) and Bristol-Myers Squibb ($BMY) ran into a buzzsaw of regulatory criticism at the FDA for their SGLT2 diabetes drug dapagliflozin, the partners are back with a fresh set of promising Phase III data on a potential combo approach using the experimental treatment.
The data they reported for the triple combination of dapagliflozin, metformin and sulfonlylurea were good: Researchers highlighted a significant drop in HbA1c in the combo arm compared to a placebo. There were significant reductions in fasting plasma glucose and body weight at 24 weeks, with blood pressure falling at 8 weeks. The dapagliflozin group, though, reported higher rates of hypoglycemia, genital infection and renal adverse events compared to the placebo group, while rates of urinary tract infection "were the same for both groups."
The partners will add the late-stage data to a large cache of trial results for this drug that also includes follow-up data used for their resubmission, which had been gathered for the campaign to persuade the FDA to change its position on the drug. Dapagliflozin was rejected after it failed to clear the agency's high safety bar on new diabetes drugs. The FDA has set a January PDUFA date on the application.
A spokesperson for Bristol-Myers Squibb tells FierceBiotech that their application for the NDA has already been completed and that this new Phase III trial was spurred by the desire to see how patients would fare with the triple combination. She declined to speculate if the data might be used in a future application.
Their setback on the SGLT2 front--covering therapies which spur the body to excrete sugar in urine--helped cloud the whole field of developers anxious to jump into the new drug category. A majority of the agency's expert panel voted against an approval in the summer of 2011 after raising concerns about cancer cases seen in studies, in addition to evidence of toxicity. Given the agency's vigilance over any safety concerns linked to diabetes treatments--a position that dates back to the storm of controversy that broke out over Avandia's side effects 5 years ago--most analysts were quick to write off any near-term approval.
The analysts were right, but the companies never gave up the faith. The setback was particularly harsh on AstraZeneca, which was fielding one bad late-stage effort after the next. European regulators, which have their own standards for this field, approved the drug as Forxiga.
If it wins a U.S. approval now, dapagliflozin will compete against Johnson & Johnson's ($JNJ) Invokana. Eli Lilly ($LLY) and Boehringer Ingelheim are also pushing for approval of empagliflozin, another SGLT2 drug that could likely crowd the market with therapies that don't offer a lot to distinguish themselves from each other. A number of analysts also have been notably unexcited by their commercial prospects.
"The improvements in glycemic control combined with the significant reduction in body weight observed in this study add to the clinical profile of dapagliflozin, specifically when used as part of a triple oral therapy regimen with metformin and sulfonylurea," said Dr. Stephan Matthaei, primary study investigator and director of the Diabetes and Metabolism Center, Quakenbrück Hospital, Quakenbrück, Germany.
- here's the press release
Special Report: Top diabetes drug pipelines of 2012 - Dapagliflozin
Editor's note: This story was changed to underscore that AstraZeneca and Bristol-Myers Squibb had already completed their resubmission of dapagliflozin and were using this latest study to test it as part of a triple combo.