Clinical Trials

Date: 2017-06-05

Type of information: Presentation of results at a congress

phase:

Announcement: presentation of results at the American Society for Microbiology (ASM) Microbe 2017 Annual Meeting

Company: Achaogen (USA - CA)

Product: plazomicin

Action mechanism:

• antibiotic. Plazomicin is a novel aminoglycoside antibiotic designed to treat serious gram-negative infections. It has shown potent bactericidal activity in nonclinical studies against important gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae (CRE). It is currently evaluated for the treatment of bacteremia and nosocomial pneumonia caused by CRE.

Disease: complicated urinary tract infections (cUTI)

Therapeutic area: Infectious diseases

Country:

Trial details: EPIC (Evaluating plazomicin in cUTI) is a multi-national, randomized, controlled, double-blind clinical trial in patients with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), which is expected to create a substantial opportunity for plazomicin to address the unmet medical need arising from multi-drug resistant (MDR) infections. EPIC is evaluating the efficacy and safety of plazomicin compared to meropenem and 609 patients were randomized to receive either plazomicin or meropenem intravenously. The primary objective of the EPIC trial is to demonstrate the non-inferiority, with a 15% non-inferiority margin as agreed by FDA, of plazomicin compared to meropenem based on the difference in composite microbiological eradication and clinical cure rate in the microbiological modified intent-to-treat (mMITT) population at both the Day 5 and test-of-cure visits. The Company expects the EPIC trial to serve as a single registration trial and support a New Drug Application (NDA) submission in the second half of 2017.

Latest news:

• • On June 5, 2017, Achaogen announced data presentations of EPIC trial at the American Society for Microbiology (ASM) Microbe 2017 Annual Meeting being held in New Orleans.
• The Phase 3 EPIC clinical trial compared plazomicin to meropenem in 609 randomized patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP). Plazomicin met the objective of non-inferiority compared to meropenem for the FDA primary efficacy endpoints, and achieved statistical superiority for the European Medicines Agency (EMA) primary efficacy endpoints.
• New analyses highlighted the efficacy of plazomicin in the subgroup of patients with bacteremia and a statistically higher rate of microbiological eradication in plazomicin-treated patients at the late follow-up visit (LFU) time point (24-32 days from first dose of intravenous study drug):
• Plazomicin demonstrated a favorable composite cure rate at Test of Cure (TOC) compared with meropenem in patients with bacteremia, with composite cure rates of 72.0% vs. 56.5% (difference [plazomicin minus meropenem]: 15.5, 95% CI: -13.7 to 41.9);
• Plazomicin demonstrated significantly higher microbiological eradication rates compared with meropenem at both the TOC and LFU visits. At the TOC visit, microbiological eradication rates were 89.5% vs. 74.6% (difference [plazomicin minus meropenem] 14.9, 95% CI: 7.0 to 22.7). At the LFU visit, microbiological eradication rates were 84.3% vs. 65.0% (difference [plazomicin minus meropenem] 19.3, 95% CI: 10.4 to 27.9).
• • On April 24, 2017, Achaogen announced multiple presentations that highlight the effectiveness of plazomicin against MDR gram-negative bacteria in multiple settings. Results were presented at the European Congress of Clinical Microbiology and Infectious Disease (ECCMID) which is being held in Vienna, Austria from April. The following data were presented during a late-breaking oral session on Saturday, April 22, 2017:
• Plazomicin versus Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP): Results of the EPIC Study Cloutier DJ, Miller LG, Komirenko AS, Cebrik DS, Krause KM, Keepers TR, Connolly LE, Wagenlehner FME
• The Phase 3 EPIC clinical trial compared plazomicin to meropenem in 609 patients with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP). As previously announced, in the EPIC trial, plazomicin achieved statistical superiority for the European Medicines Agency (EMA) primary efficacy endpoints and met the objective of non-inferiority compared to meropenem for the FDA. Additional analyses highlight the efficacy of plazomicin in important patient subgroups and at the late follow up time point (24-32 days from first dose of intravenous study drug):
• Plazomicin demonstrated superior microbiological eradication rates at test-of-cure (TOC) in both cUTI and AP subgroups. In patients with cUTI, the treatment difference in favor of plazomicin was 13.7% (95% CI, 3.1 to 24.1) and in patients with AP, the treatment difference in favor of plazomicin was 17.5% (95% CI, 5.5 to 29.5).
• A lower rate of clinical relapse at the late follow up (LFU) visit was observed for plazomicin. The clinical relapse rate was 1.8% for plazomicin vs. 7.9% for meropenem. Importantly, meropenem-treated patients with asymptomatic bacteriuria at the TOC visit had a higher likelihood of clinical relapse at the LFU visit.
• EPIC included an optional switch from intravenous to oral therapy. Efficacy by subgroups of patients who either did or did not receive oral switch therapy was presented. In the subgroup receiving intravenous only therapy the magnitude of the treatment benefit favoring plazomicin was consistent with the primary efficacy results, indicating that the oral antibiotic was unlikely to account for the observed superiority of plazomicin over meropenem at TOC.
• • On September 1, 2016, Achaogen announced that it has completed patient enrollment ahead of schedule in its Phase 3 EPIC registration clinical trial of plazomicin. The company expects to report top-line results from both the EPIC trials early in the first quarter of 2017. Achaogen is developing plazomicin to treat serious bacterial infections due to MDR Enterobacteriaceae, including carbapenem-resistant Enterobacteriaceae (CRE).
• • On June 2, 2016, Achaogen announced that it has achieved over 50 percent patient enrollment in its ongoing Phase 3 EPIC registration clinical trial of plazomicin. 

 

Is general: Yes