Merck presents results from Phase 3 trial evaluating ZERBAXA
Merck announced the first presentation of results from ASPECT-NP, a randomized, double-blind, multi-center Phase 3 clinical trial evaluating the efficacy and safety of ZERBAXA for the treatment of adult patients with ventilated nosocomial pneumonia. The results demonstrated non-inferiority of an investigational dose of ZERBAXA to meropenem, the active comparator, in the primary and key secondary endpoints. Based on these results, Merck has submitted supplemental new drug applications to the U.S. Food and Drug Administration and European Medicines Agency seeking regulatory approval for ZERBAXA for this potential new indication. The FDA Prescription Drug User Fee Act date is June 3, 2019. ASPECT-NP is a prospective, randomized, double-blind, multicenter, non-inferiority, Phase 3 clinical trial to evaluate the safety and efficacy of ZERBAXA compared to meropenem in ventilated patients diagnosed with nosocomial pneumonia, including hospital-acquired and ventilator-associated bacterial pneumonia. In the study, 726 patients were randomized 1:1 to receive an investigational 3g dose of ZERBAXA or meropenem 1g dose, administered intravenously every eight hours for eight to 14 days. Meropenem is an approved broad-spectrum injectable antibiotic widely used to treat serious infections. The primary and key secondary endpoints are Day 28 all-cause mortality and Clinical Response at test-of-cure in the intent-to-treat population. ZERBAXA was non-inferior to meropenem for the primary endpoint of 28-day all-cause mortality in the ITT population, 24.0% and 25.3% respectively, for a weighted proportion difference of 1.1%. In addition, ZERBAXA was non-inferior to meropenem in the key secondary endpoint, clinical cure at Test-of-Cure in the ITT population, 54.4% and 53.3% respectively, for a weighted proportion difference of 1.1%. Additionally, an analysis of efficacy outcomes by causative pathogens showed that clinical and microbiologic response rates for ZERBAXA were comparable to meropenem for Gram-negative respiratory tract pathogens, including Pseudomonas aeruginosa and Enterobacteriaceae. In the microbiologically evaluable population in patients with a Gram-negative pathogen at baseline clinical cure rates were 75.2% and 66.7% and microbiologic response rates were 69.9% and 62.4% for ZERBAXA and meropenem respectively. Results were consistent in the microbiologic intention-to-treat population with clinical cure rates of 73% and 67.9% for ZERBAXA and meropenem respectively. Treatment-emergent adverse events were reported in 85.9% of ZERBAXA versus 83.3% of meropenem treated patients. The incidence of treatment-related AEs was 10.5% in the ZERBAXA group and 7.5% in the meropenem group. The most commonly reported AEs with ZERBAXA were abnormal liver function tests, Clostridium difficile colitis and diarrhea. Comparable rates of AEs were reported for ZERBAXA and meropenem in critically ill patients, and approximately 1% of patients had treatment-related AEs leading to discontinuation of therapy.