FDA approves oral sulopenem for treatment of uncomplicated UTIs

Image credit: © Aquir - stock.adobe.com

Iterum Therapeutics has announced the FDA has approved the new drug application for ORLYNVAH (sulopenem etzadroxil and probenecid) for the treatment of uncomplicated urinary tract infections (uUTIs) caused by the microorganisms Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. ORLYNVAH is now approved for adult women with limited or no alternative oral antibacterial treatment options.¹

This decision from the FDA marks the first approved indication for ORLYNVAH and the first FDA-approved product for Iterum, according to the company.¹

“The FDA approval of ORLYNVAH is tremendous news for those of us who have been hoping for a new option to treat appropriate at-risk patients suffering from UTIs,” said Marjorie Golden, MD, FIDSA, site chief, infectious disease at St. Raphael Campus Yale New Haven Hospital. “Based on the totality of clinical data generated, ORLYNVAH has the potential to be an important treatment alternative for use in the community.”¹

The approval was based on positive phase 3 data from the REASSURE trial, which confirmed the safety and effectiveness of sulopenem tablets in treating urinary tract infections (UTIs), demonstrating that sulopenem was non-inferior to Augmentin. The trial’s primary criteria for non-inferiority was that the lower limit of the 95% confidence interval for effectiveness was above -10%.²

REASSURE was a randomized, double-blind, double-dummy, multicenter study. Adults aged 18 and older with UTI symptoms lasting 24 to 96 hours were eligible, provided they had at least 2 uUTI symptoms, including urgency, frequency, suprapubic pain, or pain during urination. Exclusion criteria included acute pyelonephritis symptoms, recent antibacterial treatment, use of concurrent non-study medications, urinary tract abnormalities, neurogenic bladder, long-term care residency, recent urinary instrumentation, or presence of foreign materials in the urinary tract.²

Participants were randomly assigned to receive either oral sulopenem or Augmentin twice daily for five days. Success was assessed on day 12, based on both clinical and microbiologic outcomes.²

The results demonstrated sulopenem’s non-inferiority to Augmentin, with an overall treatment difference of 6.7% in response rates, 0.6% in clinical success, and 8.5% in microbiologic success. Sulopenem showed response rates of 61.7% for overall response, 77.3% for clinical success, and 75.2% for microbiologic success, compared to 55%, 76.7%, and 66.7% respectively for Augmentin.²

Both treatments had similar tolerability, with adverse-event-related discontinuations below 1% for each. No serious adverse events (SAEs) occurred among sulopenem patients, while five were noted in the Augmentin group, though none were drug-related. Sulopenem's safety profile remained consistent with previous trials, with no new safety concerns outside those typical of β-lactams.²

“We are so pleased to have achieved this historic milestone and would like to thank all the patients, investigators, Iterum colleagues and Iterum consultants and vendors who participated in the development of ORLYNVAH. ORLYNVAH offers new hope for patients suffering from difficult-to-treat uUTIs. 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,” said Corey Fishman, CEO of Iterum Therapeutics. “As the first oral penem approved in the [United States], ORLYNVAH™ offers an excellent alternative treatment option for appropriate patients in the underserved uUTI market. With FDA approval and a clear label, we will renew our efforts to achieve a strategic transaction involving ORLYNVAH with the goal of maximizing value for our stakeholders.”¹

References:

1. Iterum Therapeutics Receives U.S. FDA Approval of ORLYNVAH™ (Oral Sulopenem) for the Treatment of Uncomplicated Urinary Tract Infections. Iterum Therapeutics. October 25, 2024. Accessed October 25, 2024. https://www.iterumtx.com/news/press-releases/detail/136/iterum-therapeutics-receives-u-s-fda-approval-of

2. Krewson C. Advisory committee meeting for oral sulopenem occurring September 9, 2024. Contemporary OB/GYN. September 6, 2024. Accessed October 25, 2024. https://www.contemporaryobgyn.net/view/advisory-committee-meeting-for-oral-sulopenem-occurring-september-9-2024