Plazomicin: the first clinical candidate from our gram-negative antibiotic discovery engine
Plazomicin, our lead product candidate, is being developed to treat serious bacterial infections due to MDR Enterobacteriaceae, including carbapenem-resistant Enterobacteriaceae (CRE), and has been evaluated in two Phase 3 clinical trials: the EPIC registration trial and the CARE descriptive trial.
The EPIC (Evaluating Plazomicin In cUTI) registration trial is intended to serve as a single pivotal trial supporting a New Drug Application (NDA) in the United States and a Marketing Authorization Application (MAA) in Europe. The Company enrolled 609 patients in the EPIC trial and, in December 2016, reported positive top-line data from both the EPIC and CARE clinical trials. In the EPIC trial, plazomicin successfully met 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.
The CARE (Combating Antibiotic Resistant Enterobacteriaceae) trial is a Phase 3 clinical trial in patients with serious bacterial infections due to CRE. Achaogen enrolled 69 patients in the CARE trial and announced top-line CARE data at the same time as the EPIC results. In the Phase 3 CARE trial, a lower rate of mortality or serious disease-related complications was observed for plazomicin compared to colistin therapy.
In October 2017, Achaogen submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for plazomicin, seeking approval to treat complicated urinary tract infections (cUTI), including pyelonephritis and bloodstream infections (BSI) due to certain Enterobacteriaceae in patients who have limited or no alternative treatment options. In December 2017, the U.S. FDA accepted for review the NDA. FDA granted the NDA Priority Review and set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 25, 2018. Achaogen also intends to submit an application for marketing authorization in the European Union (EU) in 2018.
The U.S. Food and Drug Administration has granted plazomicin Breakthrough Therapy designation for the treatment of bloodstream infections (BSI) caused by certain Enterobacteriaceae in patients who have limited or no alternative treatment options. The FDA has also granted fast track designation for the development and regulatory review of plazomicin to treat serious and life-threatening CRE infections. In addition, plazomicin has received Qualified Infectious Disease Product (QIDP) designation from the FDA. The QIDP designation was created by the Generating Antibiotic Incentives Now (GAIN) Act, which was part of the FDA Safety and Innovation Act and provides certain incentives for the development of new antibiotics, including priority review and an additional five years of market exclusivity.
The plazomicin program has been funded in part with a contract from the Biomedical Advanced Research and Development Authority (BARDA), under which $124.3 million was committed funding for the development of plazomicin.
Plazomicin is a next generation aminoglycoside designed by our scientists to overcome most clinically relevant aminoglycoside resistance mechanisms.
Aminoglycosides have been used successfully for the treatment of serious bacterial infections for more than 50 years. However, the spread of resistance to currently marketed aminoglycosides has decreased their clinical utility. We developed plazomicin by chemically improving on existing aminoglycosides, in order to overcome common aminoglycoside resistance mechanisms. These resistance mechanisms often co-travel with mechanisms. As a result, in MDR Enterobacteriaceae, including CRE, plazomicin remains active where most other antibiotics have limited potency due to resistance.
The following key attributes support the potential clinical utility and commercial value of plazomicin:
- Potent in vitro and in vivo activity in nonclinical studies against MDR Enterobacteriaceae, including CRE;
- Demonstration of non-inferiority to meropenem at day 5 and statistical superiority to meropenem at the test-of-cure (day ~17) in patients with cUTI/acute pyelonephritis (AP) infections due to Enterobacteriaceae, including fluoroquinolone-resistant and extended spectrum beta-lactamase (ESBL) producing isolates;
- Demonstration of lower 28 Day all-cause mortality and improved safety compared to colistin in patients with serious bacterial infections due to CRE;
- Potential to improve dosing strategy, which includes individualized patient dosing using our in vitro drug-monitoring assay; and
- Potential for more convenient administration as a once daily, 30-minute intravenous (IV) therapy compared to other IV antibiotics administered multiple times per day with infusion times up to two hours.
Review our literature on plazomicin.