Merck announced results from the phase 3 RESTORE-IMI 2 trial of imipenem/relebactam/cilastatin (Recarbrio™) for the treatment of adults with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP).
The multinational, double-blind, noninferiority phase 3 trial compared the efficacy and safety of imipenem/relebactam/cilastatin to piperacillin/tazobactam in 537 patients who required treatment with intravenous (IV) antibiotic therapy for HABP or VABP. Patients were randomized to receive either imipenem 500mg/cilastatin 500mg/relebactam 250mg or piperacillin 4000mg/tazobactam 500mg IV every 6 hours for 7-14 days. Both treatment arms also received open label empiric linezolid 600mg until baseline cultures confirmed absence of methicillin-resistant Staphylococcus aureus (MRSA).
Results showed that imipenem/relebactam/cilastatin was found to be noninferior to piperacillin/tazobactam. Day 28 all-cause mortality (primary end point) was observed to be 15.9% (n=42/264) with imipenem/relebactam/cilastatin vs 21.3% (n=57/267) with piperacillin/tazobactam (adjusted treatment difference: 5.3%; 95% CI: -11.9, 1.2). Moreover, a favorable clinical response at early follow-up (key secondary end point) was observed in 60.9% of patients treated with imipenem/relebactam/cilastatin vs 55.8% in the piperacillin/tazobactam arm (adjusted treatment difference: 5%; 95% CI: -3.2, 13.2).
With regard to safety, the most frequently reported drug-related adverse events (AEs) in the imipenem/relebactam/cilastatin arm were diarrhea (2%) and elevated ALT/AST (2%). Similar overall rates of AEs were reported between imipenem/relebactam/cilastatin (84.9%; n=226/266) and piperacillin/tazobactam (86.6%; n=233/269) with at least one AE. The imipenem/relebactam/cilastatin and piperacillin/tazobactam treatment arms also reported similar rates of drug-related AE (12% vs 10%, respectively), therapy discontinuations due to any AE (6% vs 8%), and therapy discontinuations due to drug-related AEs (2.3% vs 1.5%).
The Food and Drug Administration previously granted Priority Review to Recarbrio for this indication. A Prescription Drug User Fee Act (PDUFA) target date of June 4, 2020 has been set for this application.
Recarbio is currently approved to treat complicated urinary tract infections, including pyelonephritis, and complicated intraabdominal infections, in adult patients aged 18 years and older who have limited or no alternative treatment options.
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