Achaogen Begins Phase 3 Trial For New Antibiotic Plazomicin

By C. Rajan, contributing writer

Achaogen has begun enrolling patients in the Phase 3 clinical trial of its novel aminoglycoside antibiotic, plazomicin, to treat infections caused by carbapenem-resistant enterobacteriaceae (CRE).

The Phase 3 clinical trial will compare plazomicin against colistin, a well-known antibiotic. The aim of the trial is to demonstrate the superiority, measured by mortality at 28 days, of plazomicin compared with colistin in the treatment of patients with bloodstream infections or nosocomial pneumonia due to CRE. The Phase 3 trial is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. FDA.

This program has received funding in part from a contract from BARDA for up to $103.8 million.

"Commencing enrollment into this Phase 3 clinical trial of plazomicin is a significant accomplishment, as hospital based CRE infections pose a serious health threat globally," said Kenneth J. Hillan, CEO of Achaogen. "We have initiated sites in the U.S. and Europe and will further expand to sites in other important geographic regions in the coming months. The clinical advancement of plazomicin moves Achaogen closer to reaching our goal of providing effective new treatments to patients with life threatening gram-negative infections, such as CRE."

There is an urgent need for new antibiotics to treat CRE infections as these bacteria are resistant to nearly all antibiotics commonly used to treat gram-negative infections. They are also resistant to carbapenem antibiotics, which is of great concern as carbapenems are known as the last antibiotic standing in the fight against antibiotic-resistant gram-negative infections. Without any effective therapies to date, CRE infections have high mortality, with up to 50 percent mortality in patients with bloodstream infections.

California-based Achaogen, with a focus on novel antibacterials to treat multi-drug resistant (MDR) gram-negative infections, is developing plazomicin under a license agreement with Isis Pharmaceuticals. Under the terms of the agreement, Isis just received a $4 million milestone payment from Achaogen upon initiation of the Phase 3 trial, and it is eligible to receive up to $19.5 million as plazomicin advances in development. Isis is also eligible to receive royalties based on sales of plazomicin.

Plazomicin is designed to overcome common bacterial resistance mechanisms and has demonstrated potent bactericidal activity against important gram-negative pathogens, including CRE. Plazomicin is also in development for treating infections caused by certain biothreat agents, including Yersinia pestis and Francisella tularensis, which are responsible for plague and tularemia respectively. Achaogen is also developing plazomicin for the treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis in adults, following positive Phase 2 trial data.