The Medicines Company Announces Positive Results for Solo II Trial of Oritavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

The Medicines Company

today announced results for its Phase 3 SOLO clinical trial program of oritavancin, which is under investigation for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). SOLO I and SOLO II are identical multicenter, double-blind, randomized clinical trials. The Company reported positive SOLO I results in December 2012 and report similar positive SOLO II results today. In SOLO II, all protocol-specified primary and secondary efficacy endpoints were met. SOLO II demonstrated oritavancin to be non-inferior to vancomycin for both US and European regulators' required efficacy endpoints. All pre-specified endpoints were achieved, both for the Early Clinical Evaluation (ECE) (or 48-72 hour) required by the US Food and Drug Administration (FDA) and for the later Post Therapy Evaluation (PTE) (7-14 days after end of treatment) required by the European Medicines Agency (EMA). In SOLO II, adverse events were reported with similar frequencies on oritavancin and vancomycin. The combined SOLO trial data demonstrated that oritavancin and vancomycin efficacy were similar for the ECE and PTE endpoints. However, in microbiologically confirmed MRSA patients, the target population for such therapies, oritavancin-treated patients achieved the FDA-proposed endpoint of greater than or equal to 20% reduction of lesion area at ECE more frequently than vancomycin-treated patients. Under the Special Protocol Assessment (SPA) agreed with the FDA, the protocols pre-specified that MRSA patients from the SOLO studies would be pooled for the evaluation of efficacy. Commenting on the results, Clive Meanwell MD PhD, Chairman and Chief Executive Officer of The Medicines Company said: "SOLO trial data consistently show that a single dose of oritavancin given on presentation of a patient with ABSSSI to hospital can cure gram positive infections, including MRSA infections, and be at least as efficacious as multiple days of twice-daily vancomycin infusions. The safety profile also appears potentially advantageous over vancomycin. We anticipate submitting an application for oritavancin US market clearance in the fourth quarter of 2013 and a European filing in 2014." The combined SOLO studies represent the largest patient population (1,987 patients in intent-to -treat population) evaluating an anti-infective for the treatment of ABSSSI in controlled clinical trials and have assessed one of the largest subsets of patients with documented MRSA infection (405 patients). "The SOLO clinical trials are compelling due to the size of the program, the range of severe skin infection patients enrolled and the powerful and innovative drugs studied," said Ralph Corey MD, Professor of Medicine and Infectious Disease at Duke University and Principal Investigator of the SOLO Trials. "Given the high rate of efficacy the vancomycin comparator demonstrated in this and other similar trials, the most compelling finding in SOLO is in the pre-specified pooled findings that more oritavancin-treated MRSA patients had a greater than or equal to 20% reduction in their skin lesion up to 48 to 72 hours after treatment initiation. The benefit of an early, definitive and aggressive treatment strategy in seriously infected patients warrants additional study in skin and other severe infections, including those requiring prolonged periods of treatment." Primary Results in SOLO II (mITT population) ---------------------------------------------------------------------------- Timepoint Endpoint Oritavancin Vancomycin % Difference (n = 503) (n = 502) (95% CI) ---------------------------------------------------------------------------- FDA primary Early clinical endpoint: evaluation Cessation of spread, (ECE) absence of fever, no rescue antibiotics 403 (80.1%) 416 (82.9%) -2.7 (-7.5, 2.0) ------------------------------------------------------------- Greater than or equal to 20% reduction of lesion area 432 (85.9%) 428 (85.3%) 0.6 (-3.7, 5.0) ---------------------------------------------------------------------------- EMA primary Post therapy endpoint: evaluation Investigator- (PTE) assessed clinical cure 416 (82.7%) 404 (80.5%) 2.2 (-2.6, 7.0) ---------------------------------------------------------------------------- Results in patients with confirmed MRSA infections in SOLO II (Microbiological ITT population) ---------------------------------------------------------------------------- Timepoint Endpoint Oritavancin Vancomycin (n = 100) (n = 101) ---------------------------------------------------------------------------- FDA primary endpoint: Early clinical Cessation of spread, absence of evaluation (ECE) fever, no rescue antibiotics 82 (82.0%) 82 (81.2%) ------------------------------------------------------- Greater than or equal to 20% reduction of lesion area 96 (96.0%) 91 (90.1%) ---------------------------------------------------------------------------- EMA primary endpoint: Post therapy Investigator-assessed clinical evaluation (PTE) cure 84 (84.0%) 86 (85.1%) ---------------------------------------------------------------------------- Safety profiles, measured at any point up to 60 days after treatment, were similar across treatment groups in SOLO II. Overall, 50.9% of patients on oritavancin and 50.2% of patients on vancomycin were reported to experience at least one adverse event. In SOLO II, treatment emergent adverse events considered by investigators as related to study drug were reported by similar proportions of patients treated with oritavancin and vancomycin (21.7% and 25.5%, respectively). Primary Results in SOLO I and SOLO II Combined (mITT population) ---------------------------------------------------------------------------- Timepoint Endpoint Oritavancin Vancomycin % Difference (n = 978) (n = 981) (95% CI) ---------------------------------------------------------------------------- FDA primary endpoint: Early clinical Cessation of spread, evaluation absence of fever, no (ECE) rescue antibiotics 794 (81.2%) 794 (80.9%) 0.2 (-3.3, 3.7) ------------------------------------------------------------- Greater than or equal to 20% reduction of lesion area 845 (86.4%) 825 (84.1%) 2.3 (-0.9, 5.4) ---------------------------------------------------------------------------- Post therapy EMA primary endpoint: evaluation Investigator-assessed (PTE) clinical cure 794 (81.2%) 787 (80.2%) 1.0 (-2.5, 4.5) ---------------------------------------------------------------------------- Results in patients with confirmed MRSA infections in SOLO I and SOLO II Combined (MicroITT population) ---------------------------------------------------------------------------- Timepoint Endpoint Oritavancin Vancomycin % Difference (n = 204) (n = 201) (95% CI) ---------------------------------------------------------------------------- Early FDA primary endpoint: clinical Cessation of spread, evaluation absence of fever, no (ECE) rescue antibiotics 166 (81.4%) 162 (80.6%) 0.8 (-6.9, 8.4) -------------------------------------------------------------- Greater than or equal to 20% reduction of lesion area 190 (93.1%) 175 (87.1%) 6.1 (0.5, 11.6)* ---------------------------------------------------------------------------- Post therapy EMA primary endpoint: evaluation Investigator-assessed (PTE) clinical cure 170 (83.3%) 169 (84.1%) -0.7 (-7.9, 6.4) ---------------------------------------------------------------------------- *p value=0.032 When the SOLO I and SOLO II studies are combined, the safety profiles were similar across treatment groups (safety population: 976 in oritavancin, 983 in vancomycin). Overall, 55.3% of patients on oritavancin and 56.9% of patients on vancomycin were reported to experience at least one adverse event. Fewer treatment emergent adverse events considered by investigators as related to study drug were reported among patients treated with oritavancin than vancomycin (22.2% vs. 28.4% p=0.002). Proportions of patients with adverse events leading to study drug discontinuation were low and comparable between oritavancin and vancomycin (3.7% and 4.2%, respectively). The design of the Phase 3 SOLO clinical trial program was agreed to through the SPA process with the FDA and was also reviewed formally by the EMA. The pivotal Phase 3 trials are designed to support the filing of a New Drug Application in the United States as well as a Marketing Authorization Application in Europe.