WALTHAM, Mass.—Today, Entasis Therapeutics Holdings Inc. announced the initiation of the ATTACK (Acinetobacter Treatment Trial Against Colistin) Phase 3 pivotal clinical trial to evaluate ETX2514SUL, a fixed-dose combination of its broad-spectrum β-lactamase inhibitor ETX2514 with sulbactam, for the treatment of patients with pneumonia and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii.
A. baumannii is a Gram-negative bacterium that causes severe infections. It is associated with high mortality, increasing rates of antibiotic resistance and growing significance as a hospital-acquired infection, due to limited treatment options. Outbreaks of A. baumannii typically occur in intensive care units and healthcare settings with seriously ill patients, and can either cause or contribute to death. Resistance to carbapenems, a class of antibiotics commonly used for the treatment of severe bacterial infections, has grown substantially amongst Acinetobacter in the last decade.
“There are currently very limited antibiotic choices for the treatment of multidrug-resistant A. baumannii infections, and mortality rates approach 50%,” said Robin Isaacs, M.D., chief medical officer. “More than 60% of A. baumannii strains tested in the United States in 2016 were resistant to carbapenems, and in some European and Asian countries carbapenem resistance surpasses 80%. ETX2514SUL offers a precision, pathogen-targeted, approach to the treatment of A. baumannii. We look forward to enrolling patients in our ATTACK trial, which will evaluate ETX2514SUL’s efficacy and safety in the treatment of drug-resistant A. baumannii infections.”
ETX2514 is a novel, broad-spectrum inhibitor of class A, C, and D β-lactamases. ETX2514 is said to restore the in vitro activity of multiple β-lactams against Gram-negative, multidrug-resistant (MDR) pathogens. Entasis Therapeutics is initially developing ETX2514SUL for the treatment of severe A. baumannii infections. Sulbactam is a generic β-lactam which has intrinsic antibacterial 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 complicated urinary tract infections.
ATTACK is a global, two-part Phase 3 clinical trial that will enroll a total of 300 patients from 18 countries. Entasis believes this single Phase 3 trial could be sufficient to support the filing of a new drug application with regulatory authorities in both the U.S. and Europe. Subject to the necessary regulatory approvals, the clinical trial will also leverage the company’s partnership with Zai Lab for patient enrollment in China, and potentially provide early access for patients in Asia-Pacific countries. The trial will also incorporate the BioFire FilmArray Pneumonia Panel to optimize and accelerate patient enrollment.
“We are excited to initiate our global ATTACK clinical trial with the ultimate goal of obtaining regulatory approval in the U.S. and other countries,” added Manos Perros, chief executive officer, Entasis Therapeutics. “It is the culmination of extensive preclinical development and multiple Phase 1 and 2 clinical trials, which have shown that ETX2514SUL has great potential for the treatment of patients with carbapenem-resistant A. baumannii infections. We are fully funded through this study and look forward to reporting top-line data in the second half of 2020.”
The initiation of ATTACK follows the end of Phase 2 meeting with the U.S. Food and Drug Administration. ETX2514SUL has been designated a Qualified Infectious Disease Product (QIDP), and has been granted Fast Track designation.