Achaogen Submits NDA for Plazomicin for Treatment of cUTIs & Bloodstream Infections

The biopharmaceutical company Achaogen has just announced that they will be submitting a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for what they refer to as their “lead product candidate,” plazomicin, to treat complicated urinary tract infections (cUTI), including pyelonephritis and bloodstream infections (BSI) due to resistant Enterobacteriaceae that have left patients without any alternative treatment options.

Achaogen also aims to submit an application for registration in the European Union in 2018, according to the press release.

Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Enterobacteriaceae, which includes carbapenem-resistant Eneterobacteriaceae (CRE). Some CRE bacteria have developed resistance to most available antibiotics on the market, according to the Centers for Disease Control and Prevention (CDC). Thus, these infections are incredibly hard to treat, and one report found that they can result in death in about 50% of patients that become infected.

"The US Centers for Disease Control and Prevention classify CRE as an urgent public health threat due to high mortality rates and few options for treatment. CRE represents a serious and growing threat for patients in the healthcare system," said James A. McKinnell, MD, Assistant Professor of Medicine at the David Geffen School of Medicine and LA Biomed at Harbor-UCLA, told Contagion^® in an email interview.

There are 2 important trials that have been conducted to ascertain the safety and efficacy of plazomicin. The Evaluating Plazomicin In cUTI (EPIC) study assessed if monotherapy with once-daily plazomicin was safer and more effective than thrice-daily meropenem to treat patients with cUTI, including acute pyelonephritis, which is a sudden, and potentially life-threatening kidney infection that results from a UTI that begins either in the urethra or the bladder and then travels on to the kidneys. The other study, dubbed Combating Antibiotic-Resistant Enterobacteriaceae (CARE), set out to assess how safe and effective plazomicin was in comparison with colistin “when used as part of a definitive combination regimen” to treat serious CRE-associated infections.

"Clinical data from the EPIC trial showed a lower clinical relapse rate for plazomicin compared to meropenem in cUTI and a mortality benefit for plazomicin compared to colistin in the CARE trial," Dr. McKinnell told Contagion^®.

The NDA contains data from both clinical trials. According to the press release, already, the FDA has:

• Granted Breakthrough Therapy designation for plazomicin to treat BSI caused by Enterobacteriaceae in patients who have limited or no alternative treatment options
• Granted fast track designation for plazomicin’s development and regulatory review for the treatment of serious, even life-threatening CRE infections
• Given plazomicin Qualified Infectious Disease Product (QIDP) designation “with the objective of providing certain incentives for the development of new antibiotics,” which includes priority review and “an additional five years of market exclusivity.”

“The submission of the plazomicin NDA is a major step towards the potential commercialization of an important antibacterial to address multidrug-resistant gram-negative infections,” Kenneth Hillan, MB, ChB, Achaogen’s chief executive officer said in the press release.

"Plazomicin represents a critical option for CRE infections because, unlike other available agents that are based on a penicillin or beta-lactam structure, plazomicin has a completely different mechanism of action. Plazomicin may be the only drug for CRE infected patients with penicillin allergy and for particularly challenging isolates, like NDM CRE that demonstrate resistance to all penicillin or beta-lactam antibiotics," Dr. McKinnell told Contagion^®.

Feature Picture Source: Centers for Disease Control and Prevention.