FDA Advisory Committee Votes Unanimously in Favor of Plazomicin for Adults with cUTIs

The US Food and Drug Administration (FDA)’s Drug Advisory Committee voted unanimously in favor of Achaogen's plazomicin for the treatment of adults with complicated urinary tract infections (cUTIs).

The vote was 15-0; no members of the panel abstained. However, when it came to deciding if substantial evidence was provided for the safety and effectiveness of plazomicin for the treatment of bloodstream infections in patients with limited or no treatment options, the majority (11) of the committee voted against it, while 4 members voted yes.

“We are encouraged by the Committee's unanimous vote in favor of plazomicin for complicated urinary tract infections (cUTI). The discussion underscored the real-world challenges that healthcare providers face every day given limited or inadequate treatment options for certain pathogens,” Achaogen's Chief Executive Officer Blake Wise said in a recent statement.

“Regarding bloodstream infections, the Limited-Population Antibacterial Drug pathway, or LPAD, is a novel approach that enables the FDA to consider the benefits and risks for the sickest patients who have few or no available treatment options, and to approve antibiotics like plazomicin that we believe, have the potential to address these limited patient populations," he added.

Plazomicin, is a new aminoglycoside antibacterial for the treatment of serious bacterial infections due to multidrug-resistant Enterobacteriaceae, including carbapenem-resistant Enterobacteriaceae (CRE); it was designed to address current and future unmet needs when it comes to these hard-to-treat resistant infections.

On January 2, 2018, Achaogen announced that the FDA had accepted their New Drug Application (NDA) for priority review. The NDA was supported by data collected from 2 phase 3 clinical trials: Evaluating Plazomicin in cUTI (EPIC) and Combating Antibiotic-Resistant Enterobacteriaceae (CARE).

The EPIC trial evaluated the efficacy and safety of plazomicin compared with meropenem for the treatment of adult patients with cUTI or acute pyelonephritis (AP). A total of 609 patients were enrolled in the trial and positive top-line data were reported. Plazomicin met the objective of non-inferiority compared with meropenem for the FDA-specified primary efficacy endpoints; it also achieved superiority for the EMA-specified primary efficacy endpoints.

The CARE trial, which enrolled 69 participants, also reported favorable top-line data at the same time as the EPIC results. Compared with colistin therapy, investigators observed lower mortality or serious disease-related complications with the use of plazomicin.

The FDA granted Breakthrough Therapy designation for plazomicin for the treatment of Enterobacteriaceae-associated bloodstream infections in patients with limited or no alternative treatment options. Additionally, Fast Track Designation and Qualified Infectious Disease Product (QIDP) designation was also granted to plazomicin for the treatment of serious and potentially deadly CRE infections.

According to Achaogen, the following attributes prove plazomicin’s clinical utility and underscore its commercial value:

• Potent in vitro and in vivo activity in nonclinical studies against MDR Enterobacteriaceae (including CRE)
• Demonstrates non-inferiority to meropenem at day 5 and statistical superiority to meropenem at the test-of-cure day (~17) in patients with cUTI/AP infections due to Enterobacteriaceae (including fluoroquinolone-resistant and ESBL-producing isolates)
• Demonstrates lower 28-day all-cause mortality and improved safety compared with colistin in those with serious CRE-associated bacterial infections
• There is potential to improve dosing strategy (which includes individualized patient dosing using in vitro drug-monitoring assay)
• There is also the potential for more convenient administration as a once-daily, 30-minute IV therapy compared with other intravenous antibiotics administered multiple times per day with infusion times of up to 2 hours

Although the FDA is not bound by the Committee's votes, it will take their input into consideration when reviewing marketing applications.

The Prescription Drug User Fee Act (PDUFA) date for plazomicin will be June 25, 2018. If approved by this date, Achaogen expects to launch plazomicin in the United States soon after.