The US Food and Drug Administration has approved Blujepa (gepotidacin), a groundbreaking new oral antibiotic developed by GSK for the treatment of uncomplicated urinary tract infections (UTIs). This approval marks the first new class of oral antibiotics for UTIs to gain regulatory clearance in nearly 30 years, addressing a significant medical need as antimicrobial resistance continues to rise.
Blujepa is approved for female adults and pediatric patients 12 years and older (weighing at least 40 kg) with uncomplicated UTIs caused by susceptible bacteria including Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.
A Novel Mechanism of Action
As the first-in-class triazaacenaphthylene antibiotic, Blujepa works through a unique mechanism that interferes with two enzymes bacteria need for DNA replication. This dual-targeting approach may reduce the potential for resistance development, according to Dr. Tony Wood, Chief Scientific Officer at GSK.
"The approval of Blujepa is a crucial milestone with uUTIs among the most common infections in women," said Wood. "We are proud to have developed Blujepa, the first in a new class of oral antibiotics for uUTIs in nearly three decades, and to bring another option to patients given recurrent infections and rising rates of resistance to existing treatments."
Addressing a Widespread Health Burden
UTIs represent a substantial health burden, affecting up to 16 million women in the US annually. Over half of all women experience a UTI in their lifetime, with approximately 30% suffering from at least one recurrent episode. These infections cause roughly 8 million emergency room visits and 100,000 hospitalizations in the US each year.
Dr. Thomas Hooton, Professor of Clinical Medicine at the University of Miami School of Medicine, emphasized the impact of these infections: "For many, uUTIs can be a burden that severely impacts daily life. With an increasing number of patients experiencing recurrent infections, there remains a clear need for continued research of antimicrobials to help address ongoing patient challenges and the strain on healthcare systems."
Robust Clinical Evidence
The FDA approval is based on results from the pivotal Phase III EAGLE-2 and EAGLE-3 trials, which evaluated Blujepa against nitrofurantoin, a current standard of care for UTIs. In the EAGLE-2 trial, Blujepa demonstrated non-inferiority with therapeutic success in 50.6% of participants compared to 47.0% for nitrofurantoin. More impressively, in the EAGLE-3 trial, Blujepa showed statistically significant superiority, with therapeutic success in 58.5% of participants versus 43.6% for nitrofurantoin.
The clinical program involved more than 3,000 women and adolescent girls, with participants receiving either Blujepa (1,500mg orally twice daily for five days) or nitrofurantoin (100mg orally twice daily for five days).
Safety Profile
The safety and tolerability profile of Blujepa was consistent across clinical trials. The most common adverse events were gastrointestinal, with diarrhea affecting 16% of participants and nausea affecting 9%. The majority of these events were mild (69%) or moderate (28%), with severe gastrointestinal events occurring in less than 1% of all participants.
Public-Private Partnership
The development of Blujepa represents a successful public-private partnership, having been funded in part by grants from the US government's Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency.
Availability and Significance
GSK plans to launch Blujepa commercially in the second half of 2025. The approval comes at a critical time, as the number of UTIs caused by drug-resistant bacteria continues to increase, resulting in higher treatment failure rates.
While other antibiotics have recently been approved for UTIs, including Pivya (a type of penicillin) in April 2024 and Orlynvah in December 2024, Blujepa represents a truly novel class of treatment with a unique mechanism of action.
Expanding Antimicrobial Portfolio
Blujepa is part of GSK's broader efforts to address infectious diseases and antimicrobial resistance. The company has been expanding its portfolio, including the addition of tebipenem HBr, a potential treatment for complicated UTIs, through an exclusive license agreement with Spero Therapeutics in 2022.
With antimicrobial resistance posing an increasing global health threat, the approval of Blujepa represents an important advancement in the treatment arsenal for one of the most common bacterial infections affecting women worldwide.
