FDA CRL - Bristol-Myers Squibb Company

On January 17, 2012, the FDA issued a Complete Response Letter to Bristol-Myers Squibb regarding the New Drug Application for dapagliflozin, a treatment for type 2 diabetes. The agency determined the application could not be approved under the Federal Food, Drug, and Cosmetic Act due to several significant safety concerns identified during the clinical review. Primary issues included a numeric imbalance in bladder and breast cancer cases among patients taking the drug, with a particularly concerning risk estimate for bladder cancer. Additionally, the FDA identified a probable case of drug-induced liver injury meeting 'Hy’s Law' criteria. While cardiovascular safety analyses were generally reassuring, data from specific trials involving high-risk patients were inconsistent and failed to demonstrate a unique benefit that would offset the potential cancer and liver risks. To address these deficiencies, the FDA requires Bristol-Myers Squibb to submit additional clinical data, including at least 52 weeks of data from ongoing studies (Studies 18 and 19). The resubmission must include updated risk assessments for bladder cancer, a comprehensive hepatic safety review, and an updated cardiovascular meta-analysis. The agency also strongly advised the company to continue its plans for a dedicated cardiovascular outcomes trial to further define the drug’s safety profile.