Benzinga | Oct 18, 2021 04:07PM EDT

Entasis Therapeutics Announces Topline Results From Phase 3 ATTACK Trial; SUL-DUR Met Primary Efficacy Endpoint

* SUL-DUR first to achieve statistical non-inferiority in 28-day all-cause mortality in carbapenem-resistant Acinetobacter (CRAB) patients

* Statistically significant difference in clinical cure at Test of Cure vs. colistin

* Favorable safety profile with statistically significant reduction in nephrotoxicity

* Targeting NDA submission in mid-2022

* Management to host a conference call on October 19, 2021, at 8:00am ET

WALTHAM, Mass., Oct. 18, 2021 (GLOBE NEWSWIRE) -- Entasis Therapeutics Holdings Inc. (NASDAQ:ETTX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel antibacterial products, today announced topline results from its ATTACK triala global Phase 3 registrational trial evaluating the safety and efficacy of SUL-DUR versus colistin in patients with infections caused by Acinetobacter baumannii. SUL-DUR met the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections (CRABC m-MITT* population in Part A of the study), demonstrating statistical non-inferiority versus colistin. Mortality analyses favored SUL-DUR versus colistin in CRABC m-MITT and all study populations included in the topline results. At Test of Cure, there was a statistically significant difference in clinical response favoring SUL-DUR over colistin. SUL-DUR met the primary safety objective of the study achieving statistically significant reduction in nephrotoxicity.

"ATTACK was a landmark clinical trial, the first to successfully evaluate an investigational agent targeting a specific drug-resistant Gram-negative pathogen. SUL-DUR is the first investigational drug to demonstrate efficacy in a 28-day all-cause mortality trial focused on carbapenem-resistant Acinetobacter, an "Urgent" threat as designated by the CDC," said Manos Perros, Chief Executive Officer at Entasis. "The positive outcome of the ATTACK trial is the culmination of a tremendous effort by our team, and a major milestone for Entasis. We look forward to discussing our data with the regulatory agencies and preparing our first regulatory submission in mid-2022. We are grateful to our partners at Zai Lab and the investigators who made this trial possible, and to the patients and their families for their participation."

"We are immensely pleased to see the outcome of this first prospective well-controlled study of severe infections due to CRAB organisms," said Dr. Samantha Du, Chairperson and CEO at Zai Lab. "CRAB infections are among the worst bacterial infections, and safe and effective treatment options are limited. We look forward to bringing this drug to China, where CRAB infections are still frequently seen in ICUs and result in high morbidity and mortality."

"Physicians and patients need new agents for drug-resistant bacteria. Acinetobacter infections are some of the most difficult to treat, consume vast healthcare resources and inflict pain and suffering on vulnerable patients. The data from the ATTACK trial are robust and incredibly exciting, demonstrating positive safety and efficacy results, combined with favorable and meaningful clinical cure rates. If approved by regulatory agencies, SUL-DUR will address the urgent need for new treatment options for patients with life-threatening infections caused by Acinetobacter species including multidrug-resistant strains," said Keith S. Kaye, MD, MPH, Chair of the ATTACK trial Data Safety Monitoring Board and Chief, Division of Allergy, Immunology and Infectious Diseases at the Robert Wood Johnson Medical School.

ATTACK enrolled 207 patients at 95 clinical sites in 17 countries. This was a two-part trial with Part A being the randomized, comparative portion (SUL-DUR versus colistin) in patients with documented Acinetobacter baumannii hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia and Part B being an open-labeled portion (SUL-DUR only) including ABC infections resistant to or failed colistin or polymyxin B treatment. All patients received imipenem/cilastatin as background therapy. Approximately 95% of baseline Acinetobacter isolates tested were carbapenem resistant.

* SUL-DUR met the primary efficacy endpoint of 28-day all-cause mortality compared to colistin in the CRABC m-MITT population (n=125) of Part A. SUL-DUR mortality was 19.0% (12/63) compared to 32.3% (20/62) in the colistin arm (treatment difference of -13.2%; 95% CI: -30.0, 3.5)

* Similar trends were observed in 28-day and 14-day all-cause mortality favoring SUL-DUR across all study populations evaluated to date

* A statistically significant difference in clinical cure at Test of Cure (TOC) was observed with 61.9% in SUL-DUR arm compared to 40.3% in the colistin arm (95% CI: 2.9, 40.3)

* In Part B, the 28-day all-cause mortality was 17.9% (5/28) and consistent with that observed in Part A

Safety analyses were conducted in a total of 205 patients with at least one dose in Part A and Part B.

* SUL-DUR met the primary safety objective with a statistically significant reduction in nephrotoxicity as measured by the RIFLE** classification. SUL-DUR nephrotoxicity was 13.2% (12/91) versus 37.6% (32/85) in the colistin arm (p = 0. 0002)

* Overall adverse events (AEs) in the safety population were comparable between treatment groups with 87.9% (80/91) in the SUL-DUR arm versus 94.2% (81/86) in the colistin arm in Part A, 89.3% (25/28) in Part B

* Drug related AEs were 12.1% (11/91) with SUL-DUR compared to 30.2% (26/86) with colistin in Part A, 10.7% (3/28) in Part B

*Carbapenem-resistant Acinetobacter baumannii-calcoaceticus Complex Microbiologically Modified Intent-to-Treat Population

**Risk-Injury-Failure-Loss-End-stage renal disease (measured by creatinine level or glomerular filtration rate)