Plazomicin meets objective of non-inferiority in phase III trials for urinary tract infections- Achaogen

Achaogen announced that plazomicin met the objective of non-inferiority compared to meropenem for the FDA and achieved superiority for the European Medicines Agency (EMA) primary efficacy endpoints in the Phase III EPIC registration trial in patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). In addition, in the Phase III CARE trial in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE) a lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin therapy, one of the few remaining antibiotics for treatment of infections due to CRE.

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. Results for FDA pre-specified composite endpoint of clinical cure and microbiological eradication in the microbiological modified intent-to-treat (mMITT) population were as follows: Day 5: 88.0% plazomicin vs. 91.4% meropenem, indicating statistical non-inferiority. Test-of-Cure: 81.7% plazomicin vs. 70.1% meropenem, indicating statistical superiority. Results for EMA-specified endpoints of microbiological eradication at the test-of-cure visit were as follows: mMITT: 87.4% plazomicin vs. 72.1% meropenem, indicating statistical superiority. ME: 90.5% plazomicin vs. 76.6% meropenem, indicating statistical superiority. Plazomicin was well tolerated with no new safety concerns identified in the EPIC trial. Total treatment emergent adverse events (TEAEs) related to renal function were reported in 3.6% and 1.3% of patients in the plazomicin and meropenem groups, respectively. TEAEs related to cochlear or vestibular function were reported in a single patient in each of the plazomicin and meropenem treatment groups. Both events were considered mild and resolved completely.

In the Phase III CARE trial in patients with serious infections due to CRE a lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin therapy. Results from the CARE trial were as follows: Day 28 all-cause mortality or significant disease related complications (primary endpoint); 23.5% plazomicin vs. 50.0% colistin. Day 28 all-cause mortality; 11.8% plazomicin vs. 40.0% colistin. The safety profile of plazomicin was favorable to that of colistin in critically ill patients in the CARE trial.