FDA Approves First New Antibiotic in Decades for Uncomplicated UTI

The FDA on April 24 approved the oral antimicrobial pivmecillinam (Pivya) for treatment of women aged 18 years and older with uncomplicated urinary tract infections (UTI). Approval was granted to UK-based UTILITY therapeutics Ltd, according to an agency press release.¹

_{^{©Walenmarus/stock.adobe.com}}

The approval is the first in 2 decades in the US for a new antibiotic to treat UTIs, which are responsible for the greatest outpatient use of antibiotics.² Pivmecillinam is indicated for treatment of UTI caused by susceptible isolates of Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus.¹ It is estimated that one-half of all women experience at least one UTI in their lifetime.¹

“Uncomplicated UTIs are a very common condition impacting women and one of the most frequent reasons for antibiotic use,” Peter Kim, MD, MS, director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research, said in the press release.1

“Treating uncomplicated UTI remains a significant hurdle for clinicians, as there are limited options for viable first-line therapies that are effective, safe, and do not contribute to antimicrobial resistance,” UTILITY therapeutics writes on its website.² Pivemecillinam is an aminopenicillin and has been used outside the US to treat uncomplicated UTIs for more than 40 years, frequently as first-line therapy according to UTILITY.² Aminopenicillins comprise a specific class of beta-lactam antibiotics with a mechanism of action that Utility said, “may address the resistance issues facing other [antibiotic] treatments in the United States.” Pivmecillinam is the prodrug of mecillinam and is rapidly converted into mecillinam in vivo.²

The UK-based biotechnology company developed the antibiotic and acquired the US rights to pivmecillinam (oral) and mecillinam (IV), both approved in the European market.²

The FDA based yesterday’s approval on data from 3 controlled clinical trials that assessed the efficacy of pivmecillinam in women aged 18 years and older, comparing different dosing regimens to placebo, to another oral antibacterial drug and to ibuprofen.1 The primary efficacy measure for the 3 trials was the composite response rate, which included clinical cure and microbiologic response, assessed approximately 8 to 14 days after study enrollment.

In the study that compared pivmecillinam to placebo, 62% of the 137 participants in the study drug group achieved the composite response compared to 10% of the 134 who received placebo. In the comparison of pivmecillinam to another oral antibacterial drug, 72% of the 127 subjects treated with pivmecillinam vs 76% of the 132 who received the comparator drug achieved the composite response. Findings from the trial than compared pivmecillinam to ibuprofen showed that 66% of the 105 participants who received the antibiotic achieved the composite response compared to 22% of the 119 who received ibuprofen.1

According to the company’s website, the New Drug Application submitted to the US FDA for pivmecillinam included data from 6 clinical studies supporting the antibiotic’s efficacy and 12 clinical studies supporting its safety. “Through a sequence of interactions with the FDA, UTILITY has reanalyzed all available data according to the FDA 2019 uncomplicated UTI guidance. The clinical data support first-line positioning due to its benign safety profile and consistent efficacy.”

The most common side effects observed with pivmecillinam included nausea and diarrhea, according to the FDA.¹ Contraindications to use of the drug include a history of severe hypersensitivity to pivmecillinam or other beta-lactam antibacterial drugs, primary or secondary carnitine deficiency, and porphyria.¹ Labeling also recommends awareness for hypersensitivity and severe cutaneous reactions, carnitine depletion, and C difficile-associated diarrhea.¹

The antibiotic is included in clinical guidelines published by the Infectious Disease Society of America and the European Society for Microbiology and Infectious Diseases guidelines.²

Previously, pivmecillinam was granted priority review designation and qualified infectious disease product designation for this indication.¹

References

1. FDA approves new treatment for uncomplicated urinary tract infections. News release. FDA. April 24, 2024. Accessed April 25, 2024
https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-uncomplicated-urinary-tract-infections
2. Existing first-line treatments have declining utility in combating UTI, highlighting the need for innovative alternatives to better serve patients. to Utility Therapeutics. Accessed April 24, 2024.
https://utilitytherapeutics.com/our-focus/#product-pipeline