Durata Says EMA Review in Phase 3 Trial of Dalbavancin Met Primary Endpoints

Durata Therapeutics, Inc.
today announced additional preliminary, top-line results for its DISCOVER 1 ("Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response") Phase 3 study of dalbavancin, which is under investigation for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive bacteria, including MRSA (methicillin resistant Staphylococcus aureus). As reported on December 11, 2012, preliminary top-line data show that dalbavancin achieved its primary endpoint of non-inferiority at 48-72 hours after initiation of therapy, as determined by the cessation of spread of the lesion, as well as the resolution of fever. The subpopulation of patients with MRSA at baseline achieved similar results. The secondary endpoint of clinical success at the end of treatment, the expected primary endpoint for regulatory review in Europe, was also met. Statistical analyses of the results from this secondary endpoint are included below in the updated table of top-line data. Researchers were comparing two intravenous (IV) doses of dalbavancin given one week apart with twice-daily vancomycin doses for 14 days. Patients randomized to the vancomycin regimen had an option to switch to oral linezolid after three days of vancomycin treatment. The DISCOVER 1 protocol was conducted pursuant to a special protocol agreement (SPA) with the U.S. Food and Drug Administration (FDA) based on the FDA's Draft Guidance for Developing Drugs for Treatment of ABSSSI. The protocol for the trial was also designed based on scientific advice provided by the European Medicines Agency (EMA). DISCOVER 1 was a randomized, double-blind, double-dummy trial conducted in 573 patients at 92 sites in the United States, Canada, and Europe comparing dalbavancin to a regimen of vancomycin and an option for oral linezolid for the treatment of ABSSSI. Top-line Data from the DISCOVER 1 Trial Difference in point   Endpoint Dalbavancin Vancomycin/ estimates linezolid (95% Confidence interval) US Primary Early response 240/288 (83.3%) 233/285 (81.8%) 1.5% (-4.6, 7.9) Endpoint (48-72 hours)   Patients with 37/44 (84.1%) 32/39 (82.1%)   MRSA Difference in point   Endpoint Dalbavancin Vancomycin/ estimates linezolid (95% Confidence interval) EMA Primary Clinical Status 222/243 Endpoint (End of 214/246 (87.0%) (91.4%) -4.4% (-9.6, 1.6)* Treatment)   Patients with 30/35 (85.7%) 30/31 (96.8%)   MRSA Investigator   Assessment 233/246 (94.7%) 237/243 -2.8% (-6.7, 0.7) (End of (97.5%) Treatment) *adjusted for pre-specified baseline variables.   Additional information regarding the trial can be found on clinicaltrials.gov.

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