Dive Brief:
- Entasis Therapeutics released top-line data Tuesday for its beta-lactamase inhibitor for complicated urinary tract infections (UTIs).
- The privately-held drugmaker touted the fact the study met its primary endpoint of safety. The Phase 2 trial didn't have any secondary endpoints related to efficacy, but the company did share data on the overall effectiveness of its candidate.
- A Phase 3 trial in carbapenem-resistant Acinetobacter baumannii infections is planned for first quarter 2019.
Dive Insight:
The Phase 2 trial was narrowly focused on safety, comparing its inhibitor in combination with sulbactam to a placebo. Both treatment groups were also given a background therapy of imipenem/cilastatin, an antibiotic, and both control and treatment groups achieved 100% clinical success rates.
That was the expected result, CMO Robin Isaacs told BioPharma Dive, as the trial was tailored to safety testing.
Entasis set the primary endpoint for the Phase 2 trial on adverse events, which the company said the study achieved with a similar profile as the placebo.
The company also highlighted a small subset of the 80-patient study that had complicated UTIs caused by imipenem-non-susceptible pathogens. The treatment arm eradicated those pathogens in all three patients, while the placebo eradicated them in three of the five. But Isaacs said that wasn't statistically significant, nor was it meant to be in this study.
Antimicrobial resistance is a global problem. Approaches to lessen the problem include stricter control of antibiotic use in both humans and animals.
Despite this, antimicrobial resistance is increasing, challenging the usefulness of commonly-used, broad-spectrum antibiotics such as the cephalosporins and other beta-lactam antibiotics. The ability of bacteria to pass resistance between themselves adds to the challenge.
"Infections caused by Gram-negative bacteria are a major healthcare challenge today, as resistance to older antibiotics is growing," Entasis CEO Manos Perros said in a statement.
One of the ways that bacteria become resistant to beta-lactams is through production of beta-lactamase, which inactivates the antibiotic. Beta-lactamase inhibitors such as sulbactam and Entasis Therapeutics' ETX2514 aim to circumvent this route to resistance.
The company sees a potential benefit for the subgroup of patients with complicated UTIs caused by imipenem-non-susceptible pathogens.
ETX2514SUL has qualified infectious disease product designation and fast-track status for the treatment of hospital-acquired and ventilator-acquired bacterial pneumonia and bloodstream infections caused by A. baumannii.
It's one of four drugs in Entasis's pipeline, which focuses on antibacterial therapies.
The company said it expects to launch a Phase 3 trial focused on carbapenem-resistant A. baumannii infections in early 2019.