Entasis Therapeutics Announces Positive Topline Results from Phase 2 Trial of ETX2514SUL in Patients with Complicated Urinary Tract Infections including Acute Pyelonephritis
ETX2514SUL was generally well tolerated
Phase 3 to initiate first quarter 2019
WALTHAM, Mass. — August 14, 2018 —Entasis Therapeutics, a clinical-stage biopharmaceutical company focused on the discovery and development of novel antibacterial products, 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,” stated 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.
Entasis plans to present additional detail from the Phase 2 trial at an upcoming medical conference.
ETX2514 is a potent and broad-spectrum inhibitor of class A, C, and D β-lactamases. ETX2514 restores the in vitro activity of multiple β-lactams against Gram-negative, multidrug-resistant (MDR) pathogens. Entasis Therapeutics is initially developing ETX2514SUL, the combination of ETX2514 and sulbactam, for the treatment of severe A. baumannii infections. Sulbactam is a generic β-lactam which has intrinsic activity against A. baumannii but suffers from widespread β-lactamase-mediated resistance. In preclinical studies, ETX2514 restored sulbactam antibacterial activity against A. baumannii. ETX2514 has completed single- and multi-ascending dose Phase 1 trials and a Phase 2 trial, in combination with sulbactam, in cUTI. The U.S. Food and Drug Administration (FDA) has granted Qualified Infectious Disease Product (QIDP) designation and Fast Track status to ETX2514SUL for the treatment of hospital-acquired and ventilator-acquired bacterial pneumonia and bloodstream infections due to A. baumannii.
Entasis Therapeutics is developing a portfolio of innovative cures for serious drug-resistant bacterial infections, a global health crisis affecting the lives of millions of patients. Entasis’ anti-infective discovery platform has produced a pipeline of meaningfully differentiated programs which target serious bacterial infections, including ETX2514SUL (targeting Acinetobacter baumannii infections), ETX0282CPDP (targeting Enterobacteriaceae infections), a Non-Beta-lactam PBP inhibitor (targeting Gram-negative infections), and zoliflodacin (targeting Neisseria gonorrhoeae). www.entasistx.com