GSK may be an outlier in continuing to go hard on the antibiotics space, but the strategy is clearly bearing fruit. Saturday, the British Big Pharma revealed more details about the late-stage success of what could become the first new urinary tract infection (UTI) treatment in 20 years ahead of a planned FDA filing in the coming weeks.
The EAGLE-2 and EAGLE-3 phase 3 trials were expected to evaluate the antibiotic, called gepotidacin, in a total of 5,000 female adolescents and adults. But the independent data monitoring committee decided in November that enrollment could be halted early after an interim analysis of data from over 3,000 participants showed the trials had hit their primary endpoints of combined clinical and microbiological resolution.
Now, the company has revealed more details of how gepotidacin more than held its own against the commonly used UTI antibiotic nitrofurantoin. In EAGLE-2, 50.6% of patients experienced therapeutic success compared to 47% who received nitrofurantoin. In EAGLE-3, the figures were more impressive—at 58.5% and 43.6%, respectively.
When it came to resolving symptoms at 10 to 13 days after treatment, EAGLE-2 saw both antibiotics succeed in 65% of patients, while in EAGLE-3 the figures were 67.9% for the gepotidacin cohort and 63.3% for nitrofurantoin. In terms of eradicating the bacteria, EAGLE-2 showed that gepotidacin was effective in 72.5% of patients compared with 67.6% who received nitrofurantoin, with 72.2% and 57.2%, respectively, in EAGLE-3.
The data mean that as well as demonstrating “non-inferiority” to nitrofurantoin across both trials, EAGLE-3 was able to show gepotidacin’s “statistical superiority,” GSK said. As a result, the Big Pharma can continue its plans to submit the drug for approval to the FDA in the second quarter.
GSK noted that gepotidacin provided “consistent efficacy” in key subgroups when compared to the established antibiotic. These groups, all of whom are at higher risk of treatment failure, included patients with E. coli pathogens that are resistant to other antibiotics, those with a history of recurrence and individuals aged over 50.
The company announced the headline findings at the European Congress of Clinical Microbiology and Infectious Diseases in Copenhagen on Saturday, with the full results to be submitted for publication in a peer-reviewed scientific journal later this year.
“These results are a significant step forward in an area that has seen very little innovation for decades,” EAGLE-2’s principal investigator Florian Wagenlehner, M.D., said in the release.
“Gepotidacin is the first antibiotic to meet contemporary regulatory criteria, which set a high threshold for the efficacy of treatments in uUTI,” Wagenlehner added. “Gepotidacin has the potential to offer healthcare professionals another oral option to treat this common community infection.”
The most commonly reported adverse event among participants who received gepotidacin was diarrhea, which occurred in 16% of these patients, while nausea was recorded by 9%. There was one drug-related serious adverse event among patients who took gepotidacin and one among those who received nitrofurantoin.
Gepotidacin is the first in a new class of chemical antibiotics called triazaacenaphthylene bacterial topoisomerase inhibitors. While the company has been tinkering with the asset since 2007, the story really begins in 2013 with a public-private partnership between the Big Pharma and the U.S. government’s Biomedical Advanced Research and Development Authority to develop new weapons in the fight against antibiotic resistance and bioterrorism.
When you see the data coming out from gepo[tidacin], for instance—that was hard fought. The chemists wouldn't give up, the biologists wouldn't give up, the clinical people wouldn't give up." — Melanie Paff, GSK
With little return on investment for antibiotics or antifungals, GSK is one of the last major players still working on fresh candidates. But that doesn’t mean the company isn’t willing to splash the cash, paying $66 million upfront last September to license Spero Therapeutics' tebipenem HBr oral tablets, followed by $90 million to Scynexis in March to license an FDA-approved antifungal called Brexafemme for the treatment of vulvovaginal candidiasis. GSK's antibiotic for tuberculosis also proved a hit in a phase 2 trial last fall.
Talking to Fierce Biotech back in February, Melanie Paff, who heads up GSK's hepatitis B program, said antibiotics are “a really hard space to play in because the science and the biology is so difficult.”
“When you see the data coming out from gepo[tidacin], for instance—that was hard fought,” she added. “The chemists wouldn't give up, the biologists wouldn't give up, the clinical people wouldn't give up. And I'm really pleased to see that go forward and get the recognition that it deserves.”