Date: 2017-06-05
Type of
information: Presentation of results at a congress
phase: 3
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: infections due to carbapenem-resistant enterobacteriaceae (CRE)
Therapeutic
area: Infectious diseases
Country: Argentina, Brazil, Colombia, France, Germany, Greece, Israel, Italy, Mexico, Spain, Turkey, USA
Trial
details: CARE is a Phase 3 study containing a randomized open-label superiority cohort (Cohort 1) comparing the efficacy and safety of plazomicin with colistin when combined with a second antibiotic (either meropenem or tigecycline) in the treatment of patients with bloodstream infection (BSI), hospital acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP) due to CRE. An additional cohort of patients with BSI, HABP, VABP, cUTI, or AP due to CRE, not eligible for inclusion in the other cohort, will be enrolled into a single arm (Cohort 2) and treated with plazomicin-based therapy. Therapeutic drug management (TDM) will be used to help ensure that plazomicin exposures lie within an acceptable range of the target mean steady-state area under the curve (AUC).(NCT01970371)
Latest
news:
- • On June 5, 2017, Achaogen announced data presentations of the CARE trial at the American Society for Microbiology (ASM) Microbe 2017 Annual Meeting being held in New Orleans. The CARE trial compared plazomicin to colistin combination therapy on measures of efficacy and safety in bloodstream infection (BSI) or hospital acquired or ventilator associated bacterial pneumonia (HABP/VABP) due to CRE. Plazomicin demonstrated a lower rate of mortality at Day 28 or serious disease-related complications compared to colistin therapy. Among the 29 patients with BSI included in the microbiological modified intent-to-treat (mMITT) population, the mortality benefit of plazomicin vs. colistin was pronounced (7.1% all-cause mortality in the plazomicin group vs. 40.0% in the colistin group at Day 28, which represents an 82.3% relative reduction) and was maintained through Day 60 (63% reduction in the rate of death through Day 60).
- Further analyses highlighted that plazomicin was associated with a higher microbiological response rate compared to colistin and, in terms of key safety outcomes, was associated with a lower incidence and magnitude of serum creatinine increases compared to colistin:
- In patients with BSI, a favorable microbiological response at the test of cure visit of 92.9% was observed in the plazomicin group vs. 53.3% in the colistin group.
- • 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. The Phase 3 CARE clinical trial compared plazomicin to colistin combination therapy on measures of efficacy and safety in bloodstream infection (BSI) or hospital acquired or ventilator associated bacterial pneumonia (HABP/VABP) due to CRE. Plazomicin demonstrated a lower rate of mortality or serious disease-related complications compared with colistin therapy at Day 28 (50% in the colistin group versus 23.5% in the plazomicin group, which represents a 53% relative reduction). The CARE trial (cohort 1) enrolled predominantly BSI (29) vs HABP/VABP (8) patients. In the BSI population, the mortality benefit of plazomicin versus colistin was pronounced and was maintained to Day 60.
- In patients with BSI, all-cause mortality or significant complications at Day 28 was 53.3% in the colistin group versus 14.3% in the plazomicin group which represents a 73.2% relative reduction.
- Plazomicin-based therapy was associated with a 63% reduction in the rate of death in BSI patients through Day 60 compared with colistin-based therapy, with an estimated hazard ratio (plazomicin:colistin) of 0.37 (90% CI: 0.15, 0.91).
- • On February 22, 2017, Achaogen announced the achievement of a strategic milestone in the ongoing efforts to develop an assay enabling therapeutic drug management (TDM) of plazomicin. Achaogen is developing plazomicin for the potential treatment of serious bacterial infections due to MDR Enterobacteriaceae, including carbapenem-resistant Enterobacteriaceae (CRE).
- In the Phase 3 CARE trial in patients with serious infections due to CRE, an investigational assay enabling plazomicin TDM was used to help ensure that targeted exposures of plazomicin were achieved in the critically ill patients enrolled in the trial. If plazomicin is approved, Achaogen and Thermo Fisher plan to develop and have a commercial assay for plazomicin available at product launch. Achaogen plans to submit a New Drug Application (NDA) for plazomicin to the FDA in the second half of 2017. Achaogen also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2018.
- Thermo Fisher and Achaogen have been collaborating on assay development since 2015.
- • On October 24, 2016, Achaogen announced multiple data presentations from its plazomicin program at the Infectious Diseases Society of America (IDSA) IDWeek™ 2016. For the first time, the Company and its collaborators will present data from Cohort 2 of the CARE (Combating Antibiotic Resistant Enterobacteriaceae) trial of plazomicin, the Company's lead product candidate.Findings from studies, to be presented at IDWeek 2016, further supplement the evidence that plazomicin may have a role in addressing difficult-to-treat, gram-negative infections, including Carbapenem-Resistant Enterobacteriaceae (CRE). The CARE trial, a Phase 3 clinical trial in patients with serious bacterial infections due to CRE, includes a randomized cohort (Cohort 1; N=39) and a single-arm expanded eligibility cohort (Cohort 2; N=30) that includes patients with confirmed CRE. Top-line results from the CARE trial are expected to be reported, along with top-line results from the EPIC (Evaluating plazomicin in cUTI) trial, in early Q1 2017. The full CARE trial results are expected to be submitted as supportive data with the plazomicin New Drug Application (NDA) submission in the second half of 2017.• On January 11, 2016, Achaogen announced the enrollment of patients in the second cohort of its Phase 3 CARE (Combating Antibiotic Resistant Enterobacteriaceae) study, including a patient enrolled with cUTI caused by carbapenem-resistant Enterobacteriaceae (CRE).
- • On September 17, 2014, Achaogen announced that the first patient has been enrolled in the CARE Phase 3 clinical trial of plazomicin to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE).
- The Phase 3 clinical trial is designed to demonstrate the superiority, in terms of mortality at 28 days, of a plazomicin-based regimen compared with a colistin-based regimen in the treatment of patients with bloodstream infections or nosocomial pneumonia due to CRE. The trial is being conducted under a Special Protocol Assessment agreement with the FDA. Achaogen's plazomicin program is funded in part with a contract from the Biomedical Advanced Research and Development Authority (BARDA) for up to $103.8 million.
Is
general: Yes
