Entasis Therapeutics Presents Efficacy and Safety Data from Landmark Phase 3 ATTACK Trial at ECCMID 2022 Conference
In Entasis’s first oral presentation, Dr.
Results showed that this collection was 96% carbapenem- and multidrug-resistant, 84% extensively drug-resistant, and 15% pan-drug resistant. Colistin was the only comparator antibiotic tested with over 60% in vitro susceptibility. In contrast, only 4.6% of isolates had sulbactam-durlobactam (SUL-DUR) MICs >4 mg/L (above the preliminary breakpoint). Susceptibility to SUL-DUR and comparators was consistent across geographic regions and infection types, except for colistin, whose non-susceptibility ranged from 0% in
In Entasis’s second oral presentation, Dr.
The ATTACK trial was conducted to evaluate the efficacy and safety of SUL-DUR versus colistin, both in combination with imipenem/cilastatin, for patients with
- The primary efficacy endpoint, 28-day all-cause mortality (ACM) in the carbapenem resistant Acinetobacter baumannii-calcoaceticus (CRABC) m-MITT cohort (n=125) was 19.0% (12/63) and 32.3% (20/62) for SUL-DUR versus colistin, respectively (difference -13.2% [95% CI: -30.0, 3.5])
- Clinical cure rates at test-of-cure (TOC) were 61.9% (39/63) and 40.3% (25/62) for SUL-DUR versus colistin (difference 21.6 [95% CI: 2.9, 40.3])
- Treatment-related Adverse Events were 12.1% (11/91) and 30.2% (26/86) in the SUL-DUR and colistin groups, respectively
- A statistically significant reduction in nephrotoxicity was observed with SUL-DUR compared to colistin: 13.2% (12/91) versus 37.6% (32/85) (difference -24.4% [p=0.0002])
In addition to the oral presentations, five poster presentations highlighted additional SUL-DUR and ATTACK details and results.
Characterization of Co-Infecting Gram-negative pathogens isolated in addition to Acinetobacter baumannii-calcoaceticus complex (ABC) at baseline from patients enrolled in the ATTACK Phase 3 trial examined the susceptibilities of co-infecting Gram-negative pathogens from the ATTACK trial to SUL-DUR plus imipenem. 33% of m-MITT ATTACK patients were co-infected with at least one other Gram-negative pathogen. Notably, only 45% of these isolates were susceptible to imipenem alone while 73% were imipenem-susceptible in the presence of SUL-DUR. Klebsiella and Pseudomonas species were the most common co-infecting pathogens.
Sulbactam-durlobactam (SUL-DUR) in vitro dose response studies with and without imipenem or meropenem against carbapenemase-producing Acinetobacter baumannii utilizing the hollow-fiber infection model showed that, at clinically relevant exposures, SUL-DUR alone (without the presence of a carbapenem) exhibited robust killing activity against a carbapenem resistant Acinetobacter (CRAB) isolate with a
Safety profile of sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections from the global, randomized, active-controlled phase 3 trial (ATTACK) reported that 12.1% of ATTACK patients receiving SUL-DUR experienced drug-related Treatment Emergent Adverse Events compared to 30.2% in the colistin group and that nephrotoxicity (RIFLE classification) occurred significantly less often with SUL-DUR: 13.2% (12/91) vs. 37.6% (32/85), difference -24.4% [p=0.0002].
Efficacy and safety of sulbactam-durlobactam (SUL-DUR) therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections in the open label Part B of the ATTACK phase 3 trial showed a comparable 28-day ACM in Part B of ATTACK to that of Part A (17.9% vs. 19%, respectively), despite 57% of Part B patients infected with colistin-resistant Acinetobacter.
In vitro activity of sulbactam-durlobactam against Acinetobacter baumannii-calcoaceticus Complex isolates from a five-year surveillance Program (2016 –2020) highlighted SUL-DUR’s potent in vitro activity against
All Entasis ECCMID presentations are available on the Entasis website here.
Entasis is a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of novel antibacterial products to treat serious infections caused by multidrug-resistant Gram-negative bacteria. Entasis’ pathogen-targeted design platform has produced a pipeline of product candidates, including SUL-DUR (targeting Acinetobacter spp. infections), zoliflodacin (targeting Neisseria gonorrhoeae infections), ETX0282CPDP (targeting Enterobacterales infections) and ETX0462 (targeting Gram-negative infections including Pseudomonas). For more information, visit www.entasistx.com.
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Source: Entasis Therapeutics Holdings Inc.