Merck Announces Detailed Phase 3 Results of Novel Antibiotic Combination Recarbrio for Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia

Compiled by S. Li

On May 6, U.S. time, Merck & Co., Inc. (MSD) announced detailed results from the RESTORE-IMI 2 Phase 3 clinical trial evaluating the efficacy and safety of its novel antibiotic combination, Recarbrio, in adult patients with hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP). The results demonstrated that Recarbrio was statistically non-inferior to piperacillin/tazobactam (PIP/TAZ) in terms of all-cause mortality at Day 28 and clinical response, meeting both the primary and key secondary endpoints. These findings are consistent with the abstract presented at the 30th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

RESTORE-IMI 2 is a global, randomized, double-blind, non-inferiority Phase 3 clinical trial. A total of 537 patients were enrolled in the study and randomized in a 1:1 ratio to receive either Recarbrio (imipenem 500 mg/cilastatin 500 mg/relebactam 250 mg) or PIP/TAZ (piperacillin 4,000 mg/tazobactam 500 mg), administered via intravenous infusion every 6 hours for 7 to 14 days. Patients in both groups also received open-label linezolid (600 mg) until baseline cultures no longer detected methicillin-resistant Staphylococcus aureus (MRSA). The primary endpoint was all-cause mortality at Day 28, and the key secondary endpoint was clinical response at early follow-up (7 to 14 days after completion of therapy).

The results showed that Recarbrio met the primary endpoint and key secondary endpoints of the study. Specifically, the all-cause mortality rate on Day 28 was 15.9% (42/264) in the Recarbrio treatment group and 21.3% (57/267) in the PIP/TAZ treatment group (adjusted treatment difference: 5.3%; 95% confidence interval [CI]: -11.9, 1.2). The clinical response rate at early follow-up was 60.9% (161/264) in the Recarbrio treatment group and 55.8% (149/267) in the PIP/TAZ group (adjusted treatment difference: 5%; 95% CI: -3.2, 13.2).

The overall incidence of adverse events (AEs) was similar between the two treatment groups, with 84.9% in the Recarbrio group and 86.6% in the PIP/TAZ group. Furthermore, the rates of treatment discontinuation due to any AE were comparable, at 6% for the Recarbrio group and 8% for the PIP/TAZ group. The rates of treatment discontinuation due to drug-related AEs were also similar, with 2.3% in the Recarbrio group and 1.5% in the PIP/TAZ group.

Recarbrio is a fixed-dose combination antimicrobial agent composed of relebactam, imipenem, and cilastatin. Relebactam is an innovative beta-lactamase inhibitor, imipenem is an approved beta-lactam antibiotic, and cilastatin prevents the renal degradation of imipenem.

In July 2019, Recarbrio received approval from the U.S. FDA for the treatment of adult patients with complicated urinary tract infections (cUTI), including pyelonephritis caused by susceptible Gram-negative bacteria, and complicated intra-abdominal infections (cIAI), when treatment options are limited or there are no alternative therapies. In February 2020, the FDA accepted the supplemental New Drug Application (sNDA) for Recarbrio for use in adult patients with hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) and granted it priority review, with a final decision scheduled by June 4, 2020.

Reference Source:

1、Results of Phase 3 Trial Evaluating the Efficacy and Safety of Merck’s RECARBRIO™ (Imipenem, Cilastatin, and Relebactam) Versus Piperacillin and Tazobactam in Adult Patients with HABP/VABP Now Available

2、RESTORE-IMI 2: Imipenem/Cilastatin Relebactam Non-inferior to Piperacillin/Tazobactam for HABP/VABP