I am delighted to share the very exciting news that a new antibiotic, Pivya (pevmecillinam) has been approved by the US FDA for women who struggle with simple, uncomplicated UTI’s.(1) This new treatment that could ease the suffering and symptoms of millions of women in the USA struggling with Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus bladder infections.

“Uncomplicated UTIs are a very common condition impacting women and one of the most frequent reasons for antibiotic use,” said Peter Kim, M.D., M.S., director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research. Nearly half of women experience one UTI in their lifetime, resulting in more than 30 million prescriptions for antibiotics each year.(2) Unfortunately, drug resistance in e. coli infections (the most common cause of bladder infections) continues to grow with a recent report from the World Health Organization showing that 20% of these infections are drug resistant to first and second-line antibiotics.(3)

Approved for use in Europe more than 40 years ago, it has been a first line therapy for UTI in many countries with clinical cure of up to 95%.(4) In 2018, Utility Therapeutics acquired the US rights for the medication and have successfully completed the FDA review and approval process. Utility CEO Tom Hadley said “This is a product that’s been well-studied, it’s been widely used across Europe, and it’s on numerous guidelines as a first-line option.” It is also showing some promise in treated multi drug resistant infections.”(5)

Utility is one of seven companies who received funding from the AMR Action Fund which is investing more than $1 billion dollars to bring two to four antibiotics to market by 2030. “The number of safe, effective antibiotics that clinicians have at their disposal continues to dwindle in the face of rising rates of antimicrobial resistance,” said AMR Action Fund CEO Henry Skinner, PhD. “Bringing pivmecillinam to the U.S. will give clinicians an important tool to help patients suffering from urinary tract infections and support efforts to enhance global access to this drug.”(6)

Pivya’s Reduced Infection in Clinical Trials

Pivya’s efficacy was assessed in three controlled clinical trials. The primary measure of efficacy for the three trials was the composite response rate, which included clinical cure (resolution of the symptoms of the uncomplicated UTI with no new symptoms) and microbiological response (bacteria cultured from patients’ urine at trial entry was reduced). The composite response rate was assessed approximately 8 to 14 days after patients were enrolled into the studies.

Pivya Vs. Placebo

In the clinical trial comparing Pivya to placebo, 62% of the 137 subjects who received Pivya achieved the composite response compared to 10% of the 134 who received placebo.

Pivya Vs. Another Antibiotic

In the clinical trial comparing Pivya to another oral antibacterial drug, 72% of the 127 subjects who received Pivya achieved composite response compared to 76% of the 132 who received the comparator drug.

Pivya Vs. Ibuprofen

In the clinical trial comparing Pivya to ibuprofen, 66% of the 105 subjects who received Pivya achieved composite response compared to 22% of the 119 who received ibuprofen.

Side Effects & Warnings

The most common side effects of Pivya included nausea and diarrhea. Patients should not use this medication if they have a known history of severe hypersensitivity to Pivya or other beta-lactam antibacterial drugs. Patients should also not use Pivya if they have primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, or if they are suffering from porphyria.

Pivya comes with certain warnings and precautions such as hypersensitivity reactions, severe cutaneous adverse reactions, carnitine depletion, Clostridioides difficile-associated diarrhea and interference with a newborn screening test for isovaleric acidemia, a rare metabolic disorder.

Conclusion

With this announcement came celebration but also some consternation. Dr. Ashley Winter, a national expert in GSM wrote on her X account, “Cool! But, you need to spend more time fixing the label on vaginal estrogen so that UTIs are not happening in the first place. The majority of UTIs in peri & menopausal women can be prevented with low dose vaginal estrogen. That is the foundation of antimicrobial stewardship.”  While absolutely true, particularly for the millions who struggle with UTI, we must also be thankful for those few companies who are working to develop more antibiotics in this climate of intense antibiotic resistance, as well as the AMR Action Fund that is providing millions in funding. Without effective antibiotics, more and more people will suffer.

Suggested Reading

  1. FDA Press Release – FDA Approves New Treatment For Uncomplicated Urinary Tract Infections – April 24, 2024
  2. Dall C. FDA to review European-approved oral antibiotic for urinary tract infections. CIDRAP Univ. of MN – January 17, 2024
  3. Newman T. What to Know About Pivya, the New Antibiotic Treatment for UTIs. Healthline.com. April 26, 2024
  4. World Health Organization – Global antimicrobial resistance and use surveillance system (‎GLASS)‎ report December 9, 2022
  5. Zykov I, et al. Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model. International Journal of Antimicrobial Agents Volume 55, Issue 2, February 2020, 105851
  6. Utility Therapeutics Press Release UTILITY therapeutics Ltd. Announces Financing Led by the AMR Action Fund and FDA Acceptance of PIVYA New Drug Application with Priority Review January 17, 2024.