Plazomicin Succeeds in Two Pivotal Phase 3 Studies

Antibiotic developed to fight multidrug-resistant infections

Plazomicin (Achaogen, Inc.), an antibiotic being developed to fight multidrug- resistant bacterial infections, has met the primary objective of noninferiority compared with meropenem in a phase 3 registration trial among patients with complicated urinary tract infections (cUTIs) and acute pyelonephritis (AP). In addition, in a phase 3 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, one of the few remaining antibiotics for the treatment of infections due to CRE.

Achaogen plans to submit a new drug application for plazomicin to the FDA in the second half of 2017.

The EPIC (Evaluating Plazomicin In cUTI) trial was a multinational, randomized, controlled, double-blind study in adults with complicated cUTIs and AP. A total of 609 patients were randomly assigned to receive plazomicin 15 mg/kg as a once-daily 30-minute intravenous (IV) infusion or meropenem 1 g every eight hours as a 30-minute IV infusion. After a minimum of four days of IV therapy, patients who met protocol-defined criteria for improvement were allowed to step down to oral levofloxacin to complete a total of seven to 10 days of therapy (IV plus oral).

Plazomicin successfully met the objective of noninferiority compared with meropenem. Results for the FDA prespecified composite endpoint of clinical cure and microbiologic eradication in the microbiologic modified intent-to-treat population were as follows: Š

  • Day 5: 88% plazomicin vs. 91% meropenem, indicating statistical noninferiority
  • Test-of-cure: 82% plazomicin vs. 70% meropenem), indicating statistical superiority

The open-label CARE (Combating Antibiotic Resistant Enterobacteriaceae) trial evaluated the efficacy and safety of plazomicin in patients with serious bacterial infections due to CRE. The study included two groups of patients. Cohort 1 (n = 39) was a randomized, comparator-controlled cohort to compare plazomicin with colistin (either in combination with meropenem or tigecycline) for the treatment of bloodstream infection (BSI), hospital- acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP) due to CRE. Cohort 1 enrolled 30 patients with BSI and nine patients with HABP/VABP. Cohort 2 (n = 30) was a single-arm expanded access cohort to evaluate plazomicin-based therapy in patients with BSI, HABP/VABP, or cUTI due to CRE who were not eligible for enrollment in cohort 1.

A lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin. Key results from the CARE trial were as follows:

  • Day 28 all-cause mortality or significant disease-related complications (the trial’s primary endpoint): 24% plazomicin vs. 50% colistin Š
  • Day 28 all-cause mortality: 12% plazomicin vs. 40% colistin

Source: Achaogen; December 12, 2016.