Urinary tract infections (UTIs) rank as the most common bacterial infection for women worldwide. Between 50-60% of adult women experience at least one UTI in their lifetime, and approximately 25% of them suffer recurring infections, defined as two or more episodes within six months. As the prevalence of recurring infection increases with age, older women are more likely to be plagued with frequent UTIs.
The primary treatment for uncomplicated UTIs is a short regimen of one of several broad-spectrum antibiotics. Unfortunately, increasing resistance rates to these common first-line antibiotics are reducing the efficacy of these therapies, which in turn contributes to widespread antimicrobial resistance (AMR).
In fact, the primary unmet need in this space is related to the rise of antibiotic-resistant uropathogens, the bacteria responsible for UTIs. In both the community and hospital settings, the past few years have shown an increase in antibiotic resistance, coupled with higher rates of recurring infections.
The Link Between UTIs and Antimicrobial Resistance
UTIs represent a substantial health burden in the U.S., as they are the cause of more than one million ER visits and 100,000 hospitalizations each year. According to one study from 2022, the annual cost of UTI-related hospitalizations is estimated at $1.6 billion.
The uropathogens responsible for uncomplicated UTIs are both Gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, and Gram-positive bacteria, such as Staphylococcus saprophyticus and Group B streptococcus. Uropathogenic E. coli (UPEC) is the most prevalent culprit, causing an estimated 80% of community-contracted UTIs and 65% of hospital-contracted UTIs.
According to global data from the Institute of Health Metrics and Evaluation, E.coli is the pathogen responsible for the highest AMR-related mortality rate, followed by Klebsiella pneumoniae. UTIs are responsible for a significant percentage of broad-spectrum antibiotic prescriptions, which are a major cause of the spread of AMR. Unfortunately, treatment is often started without performing cultures to identify the bacteria responsible for the infection.
To complicate matters, the primarily Gram-negative bacteria that cause UTIs can become multidrug resistant via genetic mutations and gene transfer. To combat the spread of multidrug-resistant UTI isolates, new oral antibiotics are needed to support patients and mitigate the risk to public health.
New UTI Treatments on the Horizon
At long last, providers will soon have three new treatments available for the treatment of uncomplicated UTIs. The only one presently available is Iterum Therapeutics’s Orlynvah (sulopenem etzadroxil and probenecid), which became the first and only oral penem antibiotic approved by the FDA in August 2025.
Another oral antibiotic, Alembic Pharmaceuticals’ Pivya (pivmecillinam) was approved by the FDA in April 2024, and is expected to become commercially available by the end of 2025. While this drug is new in the U.S., it has been used in Europe for several decades.
And in March 2025, the FDA approved GSK’s Blujepa (gepotidacin) for the treatment of uncomplicated UTIs in females 12 and older. Blujepa is a first-in-class triazaacenaphthylene antibiotic, this approval marks the first new MoA for uncomplicated UTIs in more than 30 years.
While Blujepa is also not expected to launch until the end of 2025, many providers are eagerly awaiting this alternative drug, especially for patients whose UTIs are resistant to first-line therapies. Along with Furadantin (nitrofurantoin), legacy treatments for uncomplicated UTIs include Bactrim (trimethoprim-sulfamethoxazole) and Monurol (fosfomycin).
Blujepa works by blocking two bacterial type II topoisomerase enzymes which are needed for the bacteria to replicate. As the bacteria cannot repair the resulting DNA breaks, it ultimately dies, preventing an infection from spreading. GSK’s two global Phase 3 trials, EAGLE-2 and EAGLE-3, compared Blujepa to nitrofurantoin, the standard-of-care antibiotic. While the first trial proved that Blujepa was as effective as nitrofurantoin, in the second trial, Blujepa demonstrated statistically significant superiority to nitrofurantoin, with therapeutic success occurring in 58.5% of participants compared to 43.6%.
In a follow-up study published in the American Society for Microbiology, GSK researchers pooled the microbiology results from both trials to determine the overall incidence of drug-resistant uropathogens and evaluate gepotidacin activity against drug-resistant phenotypes. The authors concluded that “The overall prevalence of uropathogens resistant to ≥1 class of antimicrobial agents prescribed for uUTIs, together with the consistent efficacy of gepotidacin observed across these drug-resistant subgroups, suggests this first-in-class, oral, triazaacenaphthylene antibiotic may provide a new treatment option for uUTIs.”
Early Payer Response to Blujepa Messaging
So how are payers responding to GSK’s trial data and brand messaging, and what kind of coverage is expected?
According to responses recorded in MMIT’s Payer Message Monitor, payers are generally appreciative of the Blujepa’s novel MoA, calling it “interesting,” and potentially “useful to patients with allergy to standard of care.” Payers generally like that Blujepa is an oral drug, and some expressed that its approval for adolescent patients will help to expand treatment options.
Several payers agreed that Blujepa seems promising in slowing antimicrobial resistance, and one payer said that “the novel MOA will help to meet the unmet needs of women experiencing recurrent episodes and increasing rates of antibiotic-resistant uropathogens.”
Overall, however, payers seem divided on the significance of unmet need in this indication. While one payer noted that “this therapy fulfills unmet need in a patient population where options are somewhat limited,” another questioned whether there is “truly an unmet need or resistance with current therapeutic options.” Payers were also wary of Blujepa’s interaction risks, which could complicate prescribing in patients on multiple medications.
Some payers expressed concerns about the pricing of Blujepa, which has not yet been announced. Many expect that the drug will be “priced like most new branded antibiotics” and “will likely cost a lot more than current treatment options,” which is problematic in a genericized market. As one payer commented, “due to the availability of generic, cheaper options, we do not see this being utilized frequently.”
While one payer said the drug would likely be covered as a low-tier option, most payers said they needed “more real-world outcomes before we think about utilization management or coverage.”
Even though payers appreciate Blujepa’s novel MoA, they are awaiting real-world evidence of the drug’s efficacy as compared to GSK’s clinical trials. The commentary in Payer Message Monitor indicates that payers are looking for comprehensive healthcare utilization cost comparisons, as well as a more detailed explanation of how Blujepa can help prevent the spread of AMR. This data might go a long way toward persuading payers that the value of this new therapy is worth the price.
As one payer noted, “While Blujepa is expected to be priced higher than generic antibiotics like nitrofurantoin, the overall cost savings from reduced complications and hospitalizations may offset the initial expense.”
This overview of new developments in the UTI space underlines the growing importance of combatting widespread AMR with new therapies. Despite provider enthusiasm for these market entrants, however, payers remain concerned about their relatively higher cost. To improve access, manufacturers should prioritize cost-offset data about a drug’s potential to reduce hospitalizations and ER visits.
Gain key insights into payer and IDN perspectives with MMIT’s Message Monitor.
