BioPharma, Pharma

Entasis antibiotic bests last-resort drug in Phase 3 trial; FDA filing planned for 2022

Entasis Therapeutics, the former anti-infectives unit of AstraZeneca, has positive Phase 3 data for its lead program, an antibiotic that could address drug-resistant strains of Acinetobacter baumannii that contribute to hospital-acquired infections. The biotech plans to seek FDA approval in 2022.


Entasis Therapeutics has progress to report in its quest to bring patients an antibiotic that can take on drug-resistant bacteria. The company’s lead antibiotic candidate has met the main goal of a pivotal study, setting the stage for an FDA submission expected next year.

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The target pathogens, Acinetobacter baumanii, are opportunistic bacteria that mainly infect critically ill patients who are already immunocompromised. These bacteria pose a particular challenge in healthcare settings because they have the ability to quickly develop resistance to multiple existing drugs more quickly than do other bacteria. That resistance creates a need for new antibiotics for hospitals across the world. Drug-resistant infections caused by A. baumannii often lead to death.

The lead Entasis product candidate, SUL-DUR, pairs the old antibiotic sulbactam with durlobactam, a new antibiotic from the company. Waltham, Massachusetts-based Entasis is developing SUL-DUR as a treatment for infections caused by A. baumannii, including those stemming from strains that are resistant to carbapenem, a broad-spectrum antibiotic currently used.

Entasis tested SUL-DUR in a global Phase 3 clinical trial enrolling 207 patients. The study was split into two parts: Part A compared SUL-DUR to colistin, a last-resort antibiotic used to treat drug-resistant infections, and Part B, an open-label test of the drug in patients whose infections were resistant to or had failed treatment with colistin or polymyxin B, another antibiotic. The main goal of the study was to show efficacy by measuring the mortality rates from all causes after 28 days.

According to the preliminary results released Tuesday, the Entasis drug met the main goal in part A, with 12 of 63 patients dying (19%) compared to 20 deaths of the 62 patients (32.3%) in the colistin arm. In tests of the infection to determine whether a patient is cured, a clinical cure—a resolution of all signs and symptoms—was observed in 61.9% of patients treated with SUL-DUR compared to 40.3% in the colistin arm. Those results were statistically significant. In Part B, mortality was consistent with part A. In addition to the efficacy results, the Entasis drug showed better safety compared to colistin. In both parts A and B, kidney toxicity was observed in 12 of 91 patients (13.2%) compared to 32 of 85 (37.6%) in the colistin arm.

Keith Kaye, chief of the division of allergy, immunology and infectious Diseases at the Robert Wood Johnson Medical School, and the chair of the data safety monitoring board for the SUL-DUR clinical trial, said that Acinetobacter infections are among the most difficult to treat, while also representing a burden on healthcare resources and patients.

“The data from the [SUL-DUR] trial are robust and incredibly exciting, demonstrating positive safety and efficacy results, combined with favorable and meaningful clinical cure rates,” Kaye said in a prepared statement. “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.”

With the Phase 3 results in hand, Entasis plans to submit a new drug application to the FDA in mid-2022, according to an investor presentation. Entasis holds global rights to SUL-DUR, except for the Asia-Pacific region, where Zai Labs has licensed exclusive rights to develop and commercialize the drug.

Though drug-resistant bacteria present a clear medical need, large pharmaceutical companies have mostly abandoned antibiotics research. Entasis is the product of that trend. The company is the former anti-infectives unit of AstraZeneca, which spun out the division as a separate company in 2015. The biotech went public three years later, raising about $75 million. The Entasis pipeline includes Zoliflodacin, which is a late-stage drug candidate for uncomplicated gonorrhea, and the complicated urinary tract infection candidate ETX0282CPDP, which is in Phase 1 testing.

Public domain image by the CDC