Entasis Announces Positive Topline Results from Phase 2 Trial of ETX2514SUL

Entasis Therapeutics reported positive topline results from the company’s multi-national Phase 2 clinical trial of its β-lactamase inhibitor, ETX2514, in combination with sulbactam (the combination referred to as ETX2514SUL) in the treatment of complicated urinary tract infections (cUTI) including acute pyelonephritis (kidney infection) in adults. In this trial, ETX2514SUL, administered with imipenem/cilastatin (IMI), was generally well tolerated. In addition, ETX2514SUL plus IMI eradicated pathogens non-susceptible to imipenem in 3 out of 3 patients. Entasis plans to initiate a Phase 3 clinical trial focusing on carbapenem-resistant Acinetobacter baumannii infections in the first quarter of 2019.

"We are extremely pleased with the results of this study," said Robin Isaacs, Chief Medical Officer of Entasis. "Infections due to Acinetobacter baumannii are of significant concern, particularly carbapenem-resistant infections which are associated with mortality rates approaching 50% with Colistin-based treatment regimens and are particularly difficult to treat. The results of this study add to a substantial body of preclinical and clinical data supporting further development of ETX2514SUL as a treatment for serious Acinetobacter infections."

"Infections caused by Gram-negative bacteria are a major healthcare challenge today, as resistance to older antibiotics is growing," said Manos Perros, Chief Executive Officer of Entasis. "The results of this Phase 2 trial support progression of ETX2514SUL into Phase 3, an important next step in developing our pipeline of pathogen-targeted products against drug-resistant bacterial infections."

The Phase 2 double-blind, randomized, placebo-controlled clinical trial evaluated the safety and efficacy of intravenous (IV) ETX2514SUL in adult patients with complicated urinary tract infections including acute pyelonephritis. Eighty patients were randomized to receive either a dose of ETX2514SUL (ETX2514 1 g plus sulbactam 1 g) or a matching placebo every six hours for seven days. Patients in both arms also received background therapy with 500mg IV IMI every six hours. ETX2514SUL plus IMI showed similar microbiological success in the microbiologically evaluable population as placebo plus IMI (80% vs. 81%) and both treatment groups achieved 100% clinical success in the clinically evaluable population. ETX2514SUL was generally well tolerated. The adverse event profile of ETX2514SUL was similar to placebo with no serious adverse events (SAEs) reported in either arm.

In an exploratory analysis, the trial evaluated the efficacy of ETX2514SUL plus IMI against cUTIs caused by imipenem-non-susceptible pathogens. Eight patients had a cUTI caused by imipenem-non-susceptible pathogens (three in the treatment arm and five in the placebo arm). ETX2514SUL plus IMI eradicated isolates in all patients (100% [3/3]) compared to 60% (3/5) in patients receiving placebo plus IMI.

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