FDA Approves Eravacycline for Complicated Intra-Abdominal Infections

The US Food and Drug Administration (FDA) has approved Tetraphase Pharmaceuticals, Inc’s eravacycline, (XERAVA) for the treatment of complicated intra-abdominal infection (cIAI) in adults 18 years and older.

Eravacycline is a tetracycline-class antibacterial injection that has demonstrated potent activity against multidrug-resistant pathogens. In clinical trials, eravacycline was well tolerated and produced favorable results in curing patients with cIAI and demonstrated non-inferiority to ertapenem and meropenem.

The drug does not have a dose adjustment requirement when given to patients with renal impairment and the drug may be given to patients with penicillin allergies, according to a statement issued by Tetraphase.

“[Eravacycline is] a fluorocycline-type tetracycline. This drug is active against resistant Enterobacteriaceae and some gram-positive organisms as well,” explained Jason Gallagher, PharmD, clinical professor, Temple University School of Pharmacy, editor-in-chief of Contagion^® in a recent interview, “It’s fairly broad in its spectrum; it does not have activity against Pseudomonas similar to tigecycline or the other tetracyclines.”

Dr. Gallagher explained the clinical implications of eravacycline for health care providers in a recent interview. (see video below.)

The drug was assessed for cIAI in 2 Phase 3 studies called IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline.) In a previous interview with Contagion®, Guy Macdonald, president and chief executive officer of Tetraphase explained the findings of the trials.

In the first phase 3 trial, IGNITE1, 541 patients with cIAI were randomized to receive intravenous (IV) treatment with either eravacycline 1.0 mg/kg every 12 hours (n = 270) or ertapenem, 1.0 g every 24 hours (n = 271) for at least 4, 24-hour cycles. The primary endpoint was cure rates after about 1 month. The clinical cure was 86.8% and 87.6% in the eravacycline and ertapenem groups, respectively.

“In IGNITE1, twice-daily IV eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to ertapenem, was well tolerated, and achieved high cure rates in patients with polymicrobial infections (Gram-negative, Gram-positive, and anaerobic pathogens), including resistant isolates,” Macdonald explained.

In the second trial, IGNITE4 a total of 499 patients with cIAIs were randomized to IV treatment with eravacycline 1.0 mg/kg twice-daily (n = 250) or meropenem 1 g every 8 hours (n = 249). The clinical cure rates evaluated about 1 month after the start of the treatments were comparable for eravacycline and meropenem whether evaluated according to the criteria set out by the FDA (90.8% vs 91.2%) and EMA (92.4% vs 91.6%).

“In IGNITE4, a second phase 3 clinical trial in patients with cIAI, twice-daily IV eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to meropenem, was well tolerated, and achieved high cure rates in patients with polymicrobial infections (Gram-negative, Gram-positive, and anaerobic pathogens, including resistant isolates),” Mr. Macdonald explained.

Eravacycline did not receive an approval for complicated urinary tract infections.

In addition to the FDA approval for cIAI, eravacycline has also received a positive opinion from the Committee for Medicinal Products for Human Use in Europe this quarter, according to Mr. Macdonald.