A Real-world Patient Registry for Oritavancin Demonstrates Efficacy and Safety Consistent With the Phase 3 SOLO Program

Open Forum Infectious Diseases MAJOR ARTICLE A Real-world Patient Registry for Oritavancin Demonstrates Efficacy and Safety Consistent With the Phase 3 SOLO Program Mark Redell,1 Greg Moeck,2 Christopher Lucasti,3 Stephanie Durso,4 Cynthia Kennedy,1 Karen Fusaro,1 Jeff Loutit,4 and Michael Dudley4 1 The Medicines Company, Parsippany, New Jersey; 2The Medicines Company, St. Laurent, Quebec, Canada; 3South Jersey Infectious Diseases, Somers Point, New Jersey; and 4The Medicines Company, San Diego, California Background. Oritavancin is a lipoglycopeptide used in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. To characterize its use in patients in the postapproval setting, a patient registry was developed. Methods. Data collected in an ongoing retrospective observational registry are used to evaluate the utilization, outcomes, and adverse events (AEs) associated with oritavancin for the treatment of infections presumed or confirmed to be caused by gram-positive (GP) bacteria in clinical practice. Results. Data for 112 patients from 8 sites were collected. All patients received a single 1200-mg dose of oritavancin mostly in an infusion center. Infection type included cellulitis (67.0%), cutaneous abscess (21.4%), and wound (4.5%). Most patients (72.3%) received 1 or more antimicrobial agents for the index GP infection within 28 days prior to oritavancin treatment. Of positive cultures obtained prior to oritavancin administration, methicillin-resistant Staphylococcus aureus was the predominant pathogen (78.4%). A positive clinical response was observed in 92.8% of patients, and microbial eradication was observed in 90.0% of patients with post-therapy cultures. Within 28 days following oritavancin administration, 4 (3.6%) patients were hospitalized for failure of treatment of the index infection. Five (4.5%) patients experienced 1 or more possible drug-related AEs, which were consistent with types previously reported. There were no drug-related serious AEs reported. Conclusions. Clinical and microbiologic outcomes and safety of single-dose oritavancin 1200 mg were similar in this older patient population with multiple comorbid conditions to those observed in the phase 3 SOLO trials. Keywords. ABSSSI; oritavancin; registry; skin infections. Oritavancin (Orbactiv; The Medicines Company, Parsippany, NJ) is a bactericidal lipoglycopeptide antibiotic that is approved in the United States and European Union for the treatment of adult patients with acute bacterial skin and skin structure infection (ABSSSI) caused by designated gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Two identical phase 3, international, randomized, and double-blind trials (SOLO I and SOLO II) demonstrated that a single 1200-mg intravenous (IV) dose of oritavancin was noninferior to vancomycin at a dose of 1 g or 15 mg/kg every 12 hours for 7 to 10 days for the treatment of ABSSSI [1–4]. Oritavancin was introduced in the US market in late 2014. A patient registry for oritavancin (Clinical and Historic Registry and Orbactiv Medical Evaluation [CHROME]) was established to characterize the use of oritavancin in Received 1 November 2017; editorial decision 27 February 2018; accepted 16 March 2018 Correspondence: M. Redell, PharmD, The Medicines Company, 8 Sylvan Way, Parsippany, NJ 07054 (). Open Forum Infectious Diseases® © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1093/ofid/ofy051 postmarketing real-world settings. CHROME is a multicenter, multiyear, retrospective observational study to characterize the population of adult patients who have received oritavancin for the treatment of infections due to presumed or confirmed gram-positive bacteria and to describe the associated clinical and microbiologic outcomes and safety. We present results from the first phase of the CHROME registry. METHODS Study Design and Patient Population Patients who received at least 1 dose of oritavancin were eligible for enrollment. Each site enrolled at least 10 consecutive patients who had received at least 1 dose of oritavancin between October 2014 and April 2016. Sites collected patient baseline demographics, vital signs at the time of oritavancin infusion, baseline laboratory data, infection onset dates and infection classification, extent of infection area (direct measurement or comparative estimation), infection management procedures, pathogens, pre- and post-therapy antibiotics, clinical and microbiologic outcomes, date and time of oritavancin administration (including infusion start and stop times), patient disposition following oritavancin administration, and drug-related adverse events. Patients were enrolled regardless of site of care, which Oritavancin Patient Registry • OFID • 1 included infusion centers, clinics, emergency departments, and observation and inpatient hospital beds. Inclusion and Exclusion Criteria To be enrolled in CHROME, patients had to (1) be treated with oritavancin for a suspected or confirmed gram-positive infection as monotherapy or part of a broader regimen and (2) have received the last dose of oritavancin at least 60 days prior to data entry into the electronic case report form (eCRF). Waivers of informed consent were obtained from Institutional Review Boards overseeing participating sites, given the retrospective nature of the study and de-identification of patient information collected through the data entry process and final aggregation of data. Safety Assessments and Reporting Safety definitions were established by a Global Pharmacovigilance committee a priori and reflected those established for the phase 3 SOLO studies in adults with ABSSSI. Safety data were collected up to 60 days following the last dose of oritavancin. Adverse events with a reasonable possibility of a causal relationship to oritavancin, as assessed by the investigator, were reported and categorized based on their seriousness and severity according to definitions outlined in the protocol. Serious adverse events (SAEs) were defined as events that resulted in death, were life-threatening, resulted in persistent or significant disability or incapacity, required prolonged hospitalization, or were medically significant events that may have jeopardized the patient and may have required medical or surgical intervention to prevent 1 of the previously listed outcomes. SAEs, and seriousness and severity of adverse events (AEs), were collected for regulatory reporting. All SAEs, adverse events of special interest (AESIs), and pregnancies within 60 days of oritavancin infusion were reported by the i (...truncated)