AstraZeneca's former antibiotics unit claims a PhIII win in drug-resistant bacteria affecting sickly patients
The management team at Entasis, AstraZeneca’s old antibiotics unit spun out six years ago, has a new dataset it’s simply delighted to share.
Entasis revealed Phase III data outlining how an antibiotic for infections caused by Acinetobacter baumannii reached its primary endpoint of non-inferiority. Researchers compared the program — known as sulbactam-durlobactam or SUL-DUR — to the antibiotic colistin, saying their drug saw lower levels of all-cause mortality after four weeks in treatment-resistant patients.
Investors gave the news a muted golf clap, sending Entasis shares $ETTX about 3% higher in early Tuesday trading.
Acinetobacter infections generally attack critically ill patients, Entasis says, entering the bloodstream and sometimes causing pneumonia. It’s a class of bacteria that can become resistant to other types of antibiotics such as carbapenems, a commonly used medication for bacterial infections worldwide.
There are limited treatment options should patients find themselves suffering from a drug-resistant bacteria, the void Entasis hopes to fill. Its scientists are working not just on Acinetobacter infections but a whole host of other antibiotic meds, and just last month announced they would start human trials for a program that could kill a heavily scrutinized bug in Pseudomonas.
Tuesday’s data come from a study that enrolled 207 patients. Entasis set up two parts for the trial — Part A randomized the infected individuals into SUL-DUR and colistin arms, while Part B was open-label, examining SUL-DUR in previously failed treatments. Of the 125 evaluable patients in Part A, 19% of patients died on SUL-DUR after 28 days compared to 32.3% on colistin.
Because the primary endpoint was non-inferiority, Entasis did not power the study for p-values here, CEO Manos Perros said in a Tuesday morning investor call. In Part B, Entasis said it saw a similar all-cause mortality rate for SUL-DUR at 17.9% of patients.
But where Entasis sees its drug setting itself apart from competitors is in safety, particularly in the endpoint looking at nephrotoxicity. Researchers saw a statistically significant reduction in nephrotoxicity between the SUL-DUR and colistin groups in Part A: nephrotoxicity was 13.2% in the treatment arm versus 37.6% in the control, good for a p-value of p=0.0002.
“This is the key differentiator,” Entasis CMO David Altarac said on the call.
Overall adverse events were comparable between the groups, but drug-related side effects were numerically lower among those taking SUL-DUR. Only 11 of 91 patients in the active arm experienced a drug-related adverse event, compared to 26 of 86 taking colistin.
Big Pharma largely left the antibiotics space around the time AstraZeneca spun out Entasis in 2015, as dismal results continued to hound clinical trials. The field also continues to see a largely broken reimbursement system, and the WHO has warned the pipeline for new antibiotics is growing ever sparser.
But if everything goes right for Entasis, the company will be ready to submit its NDA in mid-2022.
