The FDA has granted approval to oral sulopenem (sulopenem etzadroxil/probenecid), marketed as Orlynvah by Iterum Therapeutics, for the treatment of uncomplicated urinary tract infections (uUTIs). This decision is based on data from the Phase 3 SURE 1 and REASSURE trials, which demonstrated the drug's effectiveness against common uUTI-causing pathogens, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. This approval marks a significant advancement in UTI treatment, especially considering the growing concerns about antimicrobial resistance.
Clinical Trial Results
The SURE 1 trial (NCT03354598) evaluated oral sulopenem against ciprofloxacin in patients with uUTIs, focusing on quinolone-susceptible and nonsusceptible uropathogens. The study involved 1671 patients randomized to receive either oral sulopenem or ciprofloxacin. In the quinolone nonsusceptible population, sulopenem demonstrated a significantly higher overall response rate of 62.6% compared with 36% for ciprofloxacin. Clinical success was achieved in 83% of the sulopenem group versus 62.6% in the ciprofloxacin group (p < 0.05), while microbiological success was noted in 74.1% of patients treated with sulopenem compared with 49.6% for ciprofloxacin (p < 0.05). In the quinolone-susceptible group, sulopenem met the noninferiority threshold, with an overall response rate of 66.8% compared with 78.6% for ciprofloxacin.
The REASSURE trial (NCT05584657) further assessed oral sulopenem against amoxicillin/clavulanate in a cohort of 2222 adult women with uUTIs. Participants were randomly assigned to receive either treatment for five days. Sulopenem achieved a response rate of 61.7%, while amoxicillin/clavulanate showed a rate of 55%, with a treatment difference of 6.7%. Microbiological success favored sulopenem at 75.2% compared with 66.7% for amoxicillin/clavulanate, indicating a significant advantage (p < 0.05). Both treatments were well-tolerated, with less than 1% of patients discontinuing due to adverse events, and no serious adverse events were reported for sulopenem.
Implications for Treatment
Corey Fishman, CEO of Iterum Therapeutics, emphasized the importance of Orlynvah in providing new options for patients and addressing antimicrobial resistance. He stated that the introduction of novel products like Orlynvah is an important way to combat antimicrobial resistance to other approved oral agents and offers a potential solution to patients and physicians. As the first oral penem approved in the US, Orlynvah offers an alternative treatment option for appropriate patients in the underserved uUTI market.
Approximately 40 million uUTI prescriptions are generated annually in the US, with about 1% because of pathogens resistant to standard oral antibiotics. Orlynvah is contraindicated in patients with a history of hypersensitivity to its components and may cause adverse reactions such as diarrhea and nausea. The FDA's Antimicrobial Drugs Advisory Committee (AMDAC) highlighted the need for careful post-market monitoring to prevent off-label use and ensure responsible utilization of this new antimicrobial agent.
