Merck’s Recarbrio Receives FDA Priority Review for New Indication in Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia
Feb 06, 2020 10:19
CST Updated
10:19
MSD
Pharmaceutical R&D and Manufacturer
FDA
U.S. Food and Drug Administration
February 06, 2020 /BioValleyBIOON/ -- Merck & Co. recently announced that the U.S. Food and Drug Administration (FDA) Compound formulation acceptedAntibioticsThe supplemental new drug application (sNDA) for Recarbrio (imipenem/cilastatin/relebactam) has been granted priority review. This sNDA seeks approval for Recarbrio for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in adult patients caused by certain susceptible Gram-negative bacteria.BacteriaHospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP).FDAThe Prescription Drug User Fee Act (PDUFA) target date for this sNDA has been set as June 4, 2020.
Dr. Nicholas Kartsonis, Senior Vice President of Clinical Research, Infectious Diseases and Vaccines at Merck Research Laboratories, stated: “This sNDA reinforces Merck’s continued commitment to researching and developing potentialAntibioticstreatment regimens to address unmet medical needs. We remain steadfastly committed to evaluating treatments for infections caused by certain Gram-negative pathogens.”
This sNDA is based on the results of the pivotal Phase III RESTORE-IMI 2 trial. This was a global, multicenter, randomized, non-inferiority study evaluating the efficacy and safety of Recarbrio for the treatment of adult patients with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). Last October, MSD announced that the study met its primary and secondary endpoints: in the modified intent-to-treat (MITT) population, early follow-up demonstrated that Recarbrio was statistically non-inferior to piperacillin/tazobactam with respect to all-cause mortality and clinical response at Day 28. The incidence of adverse events observed in the two groups was similar. The full data from the study will be presented at the 30th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2020), held in Paris, France, from April 18 to 21, 2020.
In the United States, Recarbrio 1.25g injection was approved in July this yearFDAapproved through the priority review program for the treatment of adults aged 18 years and older with limited or no alternative treatment options, for the treatment of complicated urinary tract infections (cUTI, including pyelonephritis) and complicated intra-abdominal infections (cIAI) caused by certain susceptible Gram-negative bacteria.
Recarbrio is a new fixed-dose combination antibiotic administered via intravenous infusion. In July 2019, Recarbrio was approved by the U.S.FDAapproved through the Priority Review program for the treatment of complicated urinary tract infections (cUTI, including pyelonephritis) and complicated intra-abdominal infections (cIAI) caused by certain susceptible Gram-negative bacteria in patients aged 18 years and older who have limited or no alternative therapeutic options.
Recarbrio is a combination of imipenem-cilastatin and relebactam. The imipenem/cilastatin combination is a compound formulation that has been in use for decades.AntibioticsThe product, branded as Primaxin/Tienam (Chinese brand name: Taineng), is commonly used to effectively treat variousBacteriaSexual infection, in which imipenem is a carbapenem antibiotic, and cilastatin is a renal dehydropeptidase inhibitor that lacks antibacterial activity but can limit the renal metabolism of imipenem.
Relebactam is a novel β-lactamase inhibitor belonging to the diazabicyclooctane class, with broad-spectrum activity against β-lactamases, including Class A (extended-spectrum β-lactamases and KPC) and Class C (AmpC enzymes). Relebactam protects imipenem from degradation by certain serine β-lactamases. When used in combination with relebactam, Gram-negative bacterial strains that are resistant to imipenem become more susceptible to it.
Relebactam molecular structure (Image source: medchemexpress.cn)
Currently, relebactam is being evaluated in combination with imipenem-cilastatin for the treatment of certain Gram-negativeBacteriaTreatment of infection. Previously,FDAThe combination therapy of relebactam with imipenem-cilastatin for intravenous treatment of cUTI, cIAI, HABP, and VABP has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations.
The approval of Recarbrio for the indications of cUTI and cIAI was based on the positive results from the pivotal Phase III clinical study, RESTORE-IMI 1. This study was conducted in adult patients with cUTI and cIAI. The results demonstrated that, for the treatment of imipenem-resistant infections, the relebactam plus imipenem/cilastatin regimen (IMI/REL) exhibited a favorable overall response rate and lower nephrotoxicity compared to the colistin plus imipenem/cilastatin regimen (COL+IMI) in the microbiologically modified intent-to-treat (mMITT) population. Specific data were as follows: (1) Overall response rate: 71.4% for IMI/REL versus 70.0% for COL+IMI; (2) Clinical response rate at Day 28: 71.4% for IMI/REL versus 40.0% for COL+IMI; (3) All-cause mortality at Day 28: 9.5% for IMI/REL versus 30.0% for COL+IMI; (4) Incidence of drug-related adverse events: 16.1% for IMI/REL versus 31.3% for COL+IMI; (5) Incidence of nephrotoxicity: 10% for IMI/REL versus 56% for COL+IMI. (Bioon.com)