Express for drug-resistant bacterial infections, innovative antibiotic compound therapy Phase 3 clinical results are positive

▎Editor of WuXi AppTec content team On October 19, 2021, Zai Lab and Entasis Therapeutics announced that the antibiotic combination therapy sulbactam-durlobactam (SUL-DUR) has obtained positive results in a phase 3 clinical trial
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In patients with carbapenem-resistant Acinetobacter (CRAB), compared with polymyxin, SUL-DUR treatment reaches a statistically significant non-inferiority standard, and has better safety
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Acinetobacter is a gram-negative bacterium and an opportunistic human pathogen.
It mainly infects critically ill patients and usually causes severe pneumonia and bloodstream infections; but it can also infect other body parts, such as the urinary tract and Skin
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Acinetobacter is considered a serious global public health threat, partly because it can acquire multi-drug resistance at a rate never seen in other bacteria
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Due to limited treatment options, the morbidity and mortality of these infections are high
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According to CARSS's 2019 annual report, there were more than 230,000 cases of Acinetobacter infection in China in 2019, and the actual incidence is estimated to be much higher than this number
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Given the best treatment, the mortality rate of Acinetobacter baumannii infection in China is about 50%
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Durlobactam is a β-lactamase inhibitor that has unique activity against Acinetobacter organisms (including carbapenem resistant strains) when combined with sulbactam
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Zai Lab has the exclusive license to develop and commercialize SUL-DUR in Mainland China, Hong Kong, Taiwan, Macau, South Korea, Vietnam, Thailand, Cambodia, Laos, Malaysia, Indonesia, Philippines, Singapore, Australia, New Zealand and Japan
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Image source: 123RF The trial enrolled 207 patients
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The trial consists of two parts, Part A is a randomized control part (SUL-DUR vs.
Polymyxin), and part B is an open label part (SUL-DUR only)
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The key results of the trial are as follows: In Part A (n=125), compared with polymyxin, SUL-DUR reached the primary efficacy endpoint of 28-day all-cause mortality, with a mortality rate of 19.
0% (12/63).
The colistin group was 32.
3% (20/62)
.

In all study populations evaluated so far, 28-day and 14-day all-cause mortality rates were also observed in favor of SUL-DUR.
The difference in clinical cure rate observed in clinical cure evaluation was statistically significant.
SUL- The DUR group was 61.
9%, while the polymyxin group was 40.
3% (95% CI: 2.
9, 40.
3).
In Part B, the 28-day all-cause mortality rate in the SUL-DUR group was 17.
9% (5/28), which is the same as Part A The observed results are consistent with SUL-DUR reaching the main safety goal, and its nephrotoxicity is statistically significantly reduced
.

The nephrotoxicity in the SUL-DUR group was 13.
2% (12/91), while the polymyxin group was 37.
6% (32/85) (p=0.
0002).
The overall adverse events (AE) in the safe population were among the treatment groups Comparable, the SUL-DUR group was 87.
9% (80/91), while in the polymyxin group, part A was 94.
2% (81/86) and part B was 89.
3% (25/28)
.

Mr.
Manos Perros, CEO of Entasis, said: “SUL-DUR is the first investigational drug that has been proven effective against carbapenem-resistant Acinetobacter in a prospective, controlled clinical study. .

Based on the reliable data obtained from the ATTACK trial, we believe that once approved, SUL-DUR can become an important option for the treatment of Acinetobacter, including the treatment of multidrug-resistant infections
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Dr.
Du Ying, founder, chairman and CEO of Zai Lab, said: “We are very pleased to see this first prospective, controlled study of severe infections caused by carbapenem-resistant Acinetobacter.
Positive results
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Carbapenem-resistant Acinetobacter infection is one of the most serious bacterial infections, and safe and effective treatment options are limited
.

This type of infection is still common in intensive care units and is accompanied by high morbidity and mortality.
We look forward to bringing this drug to China
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"References: [1] Zai Lab and Entasis Therapeutics announced the positive key results of the SUL-DUR Phase 3 clinical study ATTACK.
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.

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in the
article .
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.

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