The drug has the potential to treat certain multi-drug resistant gram-negative pathogens like CRE.
Achaogen Inc. has announced the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for plazomicin to treat complicated urinary tract infections (cUTI), including pyelonephritis and bloodstream infections (BSI) due to certain Enterobacteriaceae in patients with limited or no alternative treatment options.
The NDA includes data from 2 phase 3 clinical trials, EPIC and CARE, that evaluated the safety and efficacy of plazomicin in patients with serious infections caused by gram-negative pathogens like carbapenem-resistant Enterobacteriaceae (CRE).
"Serious infections due to multi-drug resistant (MDR) bacteria are extensive and on the rise, and there are limited or inadequate therapeutic options — leading to high rates of mortality," Kenneth J. Hillan, M.B. Ch.B., chief executive officer, Achaogen, told MD Magazine. "We believe that plazomicin represents an important potential option against the serious threat of MDR facing our hospitals."
The positive results from the EPIC trial demonstrated that plazomicin successfully achieved primary endpoints in patients with cUTI, meeting the objective of non-inferiority compared to meropenem for the FDA-specified primary efficacy endpoints, and achieved superiority for the EMA-specified primary efficacy endpoints. Total treatment emergent adverse effects related to renal function were reported in 3.6% and 1.3% of patients in the plazomicin and meropenem groups, while total treatment emergent adverse effects related to cochlear or vestibular function were reported in a single patient in each treatment group. Both events were considered mild and resolved.
The phase 3 CARE trial showed a 71% relative reduction in day 28 all-cause mortality compared to colistin in patients with serious CRE infections. In patients with serious infections due to CRE, a lower rate of mortality or serious disease-related complications were observed for plazomicin compared with colistin. In critically ill patients, the safety profile of plazomicin was favorable to that of colistin.
Overall, plazomicin was well tolerated in both trials and showed improved overall safety.
The FDA granted breakthrough therapy designation for plazomicin for the treatment of BSI caused by certain Enterobacteriaceae in patients with limited or no treatment options.
Plazomicin was also granted fast track designation for the development and regulatory review to treat serious and life-threatening CRE infections.
It’s received Qualified Infectious Disease Product (QIDP) designation from the FDA with the objective of providing certain incentives for the development of new antibiotics, including priority review and an additional 5 years of market exclusivity.
Achaogen anticipates submitting an application for registration in the European Union (EU) in 2018.
A press release was made available.