The Medicines Company has announced positive results from an interim analysis of the TANGO-2 trial of its fixed-dose, investigational antibiotic combination, meropenem-vaborbactam. Randomization in the trial was stopped early, following a recommendation by the TANGO-2 independent Data and Safety Monitoring Board (DSMB) based on an analysis of 72 patients, including 43 patients with microbiologically evaluable carbapenem-resistant Enterobacteriaceae (CRE) infections of blood, lung, urinary tract and abdominal organs. The DSMB concluded that a risk-benefit analysis of available data no longer supported randomization of additional patients to the best available therapy comparator arm. The Company will continue to enroll patients into an amended, single-arm study protocol for treatment with meropenem-vaborbactam at selected sites.
The Company expects that data from the TANGO-2 trial will be presented at a future medical conference and published in a peer-reviewed journal.
The Company also announced that it has selected, and both US and European regulatory authorities have accepted, VabomereTM as the US and European trade name for meropenem-vaborbactam, assuming marketing applications are approved. Previously, meropenem-vaborbactam was commonly referred to as “Carbavance.”
The DSMB’s recommendation to discontinue randomization into the TANGO-2 trial was based on the results of an interim analysis of data from TANGO-2, which showed that, for efficacy, statistically-significant differences favor meropenem-vaborbactam over best available therapy for clinical cure at the test of cure visit in the protocol-specified primary population (all patients with microbiologically-evaluable CRE). Mortality rates were also lower among patients treated with meropenem-vaborbactam. The DSMB also noted a clear difference in renal toxicity, with lower rates of renal adverse events and serum creatinine increases among patients treated with meropenem-vaborbactam than best available therapy – particularly among patients receiving colistin and aminoglycosides.
Keith S. Kaye, MD, MPH, Professor of Medicine at the University of Michigan, and the principal investigator for TANGO-2, stated, “We are grateful for the oversight of the DSMB and for their recommendations. This real-world study involving critically-ill, complex patients met its aims at this interim analysis. Results of TANGO-2 are thoroughly impressive and demonstrate notable efficacy and safety advantages of meropenem-vaborbactam compared to ‘best available therapy’ in the treatment of patients with selected serious infections, suspected or known to be due to CRE. We expect to present details of the TANGO-2 data in a peer-reviewed publication and at a medical conference in the future.”
Michael Dudley, PharmD, senior vice president, Head of R&D and Co-Leader for The Medicines Company’s Infectious Disease Business, added, “We are grateful to the patients and families that participated in this trial. We have followed the DSMB’s advice and ended randomization into the trial. We are amending the study protocol to now enroll patients only into the meropenem-vaborbactam treatment group. We expect this extension of TANGO-2 will build on our body of knowledge of CRE patients – which includes information from a case series of 256 patients managed at many of the TANGO-2 study sites prior to the start of the trial, which was recently published in the journal, Open Forum Infectious Diseases. The need for data on the efficacy and safety of new therapies for treating CRE is well recognized and has been highlighted by both the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), each of which has prioritized CRE infections at the top of its list of antimicrobial drug resistance threats worldwide. We are very pleased with the data on Vabomere from TANGO-2.”
TANGO-2 is a multi-center, randomized, open-label Phase III clinical trial of meropenem-vaborbactam versus “best available therapy” in patients with serious infections (complicated urinary tract infections (cUTI), bacteremia, hospital-acquired or ventilator-associated bacterial pneumonia, and complicated intraabdominal infections) suspected or documented to be caused by CRE. Patients with CRE were randomized to receive either meropenem-vaborbactam monotherapy or the best available therapy for up to 14 days. Patients randomized to the best available therapy arm of the trial were given antimicrobial therapy selected for each patient by the investigator based on laboratory and other patient data, and thus represents the current standard of care used for the treatment of CRE infections.