The U.S. Food and Drug Administration (FDA) has approved Orlynvah (sulopenem etzadroxil and probenecid) for the treatment of uncomplicated urinary tract infections (uUTIs) in adult women with limited treatment options. Developed by Iterum Therapeutics, Orlynvah is the first oral penem antibiotic to receive FDA approval, marking a significant advancement in the treatment of resistant uUTIs.
Clinical Trial Data
The approval of Orlynvah is supported by data from two Phase 3 clinical trials, SURE 1 and REASSURE. These randomized, double-blind studies evaluated the efficacy and safety of Orlynvah compared to ciprofloxacin and Augmentin (amoxicillin/clavulanate), respectively.
- SURE 1: Demonstrated the superiority of Orlynvah over ciprofloxacin in treating fluoroquinolone-resistant infections. The composite response rate for Orlynvah was 48% compared to 33% for ciprofloxacin.
- REASSURE: Showed non-inferiority and statistical superiority of Orlynvah compared to Augmentin in Augmentin-susceptible populations. The composite response rate for Orlynvah was 62% compared to 55% for Augmentin.
Addressing Antimicrobial Resistance
Uncomplicated UTIs are highly prevalent, affecting approximately 50% of women at least once in their lifetime and resulting in an estimated 10.5 million doctor visits annually in the U.S. The rise of antimicrobial resistance has complicated treatment, with common bacteria like E. coli becoming less susceptible to commonly prescribed antibiotics.
Orlynvah's approval addresses this critical need, offering an alternative oral antimicrobial option, especially against fluoroquinolone-resistant infections. According to Keith Kaye, an infectious disease physician scientist at Rutgers University, Orlynvah is effective against both ESBL-producing E. coli and quinolone-resistant organisms, which are increasingly prevalent in both hospital and community settings.
Mechanism of Action
Orlynvah contains two active ingredients: sulopenem etzadroxil and probenecid. Sulopenem, a penem antibiotic, inhibits bacterial cell wall synthesis, leading to bacterial cell death. Probenecid inhibits the kidneys from eliminating sulopenem, prolonging the antibiotic's presence in the body.
Considerations for Prescribing
Orlynvah is specifically approved for uncomplicated UTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women with limited or no alternative treatment options. Healthcare providers are advised to avoid off-label use to preserve its effectiveness and prevent further antimicrobial resistance.
Florian Wagenlehner, a urologist at Justus-Liebig University Giessen, suggests that Orlynvah's use should be restricted to cases with high resistance or when patients cannot tolerate first-line antibiotics, emphasizing its role for a niche patient group.
Potential Side Effects
Common adverse reactions reported in clinical trials include diarrhea, nausea, headache, vomiting, and fungal infections of the vulva and vagina. More serious side effects may include hypersensitivity reactions and Clostridium difficile-associated diarrhea.
Impact on Treatment Landscape
Orlynvah represents a significant advancement in the treatment of uncomplicated UTIs, providing a much-needed oral option for patients with resistant infections. Its availability has the potential to reduce hospitalizations and improve patient outcomes, particularly in cases where intravenous penem antibiotics were previously required. However, responsible use and adherence to antimicrobial stewardship principles are essential to minimize the development of further resistance.
