FDA Approves Orlynvah for Uncomplicated Urinary Tract Infections in Women with Limited Oral Antibiotic Options
Key Insights
The FDA has approved Orlynvah (sulopenem etzadroxil and probenecid) for treating uncomplicated urinary tract infections (search) (uUTIs) in adult women with limited oral antibacterial options.
Orlynvah, the first oral penem antibiotic approved in the U.S., targets uUTIs caused by Escherichia coli (search), Klebsiella pneumoniae (search), or Proteus mirabilis (search).
Clinical trials (SURE 1 and REASSURE) demonstrated Orlynvah's superiority to ciprofloxacin in fluoroquinolone-resistant infections and non-inferiority/superiority to Augmentin™.
The U.S. Food and Drug Administration (FDA) has granted approval to Orlynvah (sulopenem etzadroxil and probenecid) for the treatment of uncomplicated urinary tract infections (search) (uUTIs) in adult women who have limited or no alternative oral antibacterial treatment options. This marks the first FDA-approved product for Iterum Therapeutics (search) and introduces a novel oral penem antibiotic to the U.S. market.
Clinical Efficacy and Safety
The FDA's decision was supported by data from a comprehensive clinical development program, including two pivotal Phase 3 clinical trials, SURE 1 and REASSURE. These trials evaluated the safety and efficacy of Orlynvah in comparison to ciprofloxacin (SURE 1) and Augmentin™ (REASSURE) in adult women diagnosed with uUTIs.
SURE 1 demonstrated Orlynvah's superiority over ciprofloxacin in treating fluoroquinolone-resistant infections. REASSURE indicated non-inferiority and statistical superiority to Augmentin™ within the Augmentin™-susceptible population. In both trials, Orlynvah was generally well-tolerated.
Marjorie Golden, MD, FIDSA, Site Chief, Infectious Disease, St. Raphael Campus Yale New Haven Hospital, noted, "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. Based on the totality of clinical data generated, Orlynvah has the potential to be an important treatment alternative for use in the community."
Dosage and Administration
Orlynvah is administered orally as one tablet twice daily for a duration of 5 days. It is specifically indicated for uUTIs caused by designated microorganisms, including Escherichia coli (search), Klebsiella pneumoniae (search), and Proteus mirabilis (search).
Limitations of Use
It is important to note that Orlynvah is not indicated for the treatment of complicated urinary tract infections (search) (cUTIs) or as a step-down treatment following intravenous antibacterial treatment for cUTIs. Additionally, it is not approved for complicated intra-abdominal infections (cIAIs) or as a step-down therapy after intravenous antibacterial treatment of cIAIs.
Understanding Uncomplicated UTIs
UTIs are among the most prevalent bacterial infections, with uUTIs primarily affecting women. Approximately 60% of women will experience a uUTI during their lifetime, and up to 40% of those with a history of uUTIs will face recurrence. In the United States, around 40 million uUTI prescriptions are generated annually, with an estimated 1% of these infections caused by pathogens resistant to commonly available oral antibiotics.
Mechanism of Action
Orlynvah is a combination of sulopenem etzadroxil, a penem antibacterial, and probenecid, a renal tubular transport inhibitor. Sulopenem exhibits potent activity against Enterobacterales species, including those that encode extended-spectrum beta-lactamase (ESBL) or AmpC-type beta-lactamases, which confer resistance to third-generation cephalosporins.
Contraindications and Warnings
Orlynvah is contraindicated in patients with a history of hypersensitivity to its components (sulopenem etzadroxil and probenecid) or other beta-lactam antibacterial drugs, those with known blood dyscrasias, or patients with known uric acid kidney stones. Concomitant use of Orlynvah and ketorolac tromethamine is also contraindicated.
Warnings and precautions include the potential for hypersensitivity reactions, Clostridioides difficile-associated diarrhea (CDAD), and exacerbation of gout. Appropriate therapy should be instituted for patients with a known history of gout.
Adverse Reactions
The most common adverse reactions (≥2%) reported in patients treated with Orlynvah were diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting.
Drug Interactions
Concomitant use of Orlynvah with ketoprofen is not recommended. Clinicians should consult the full prescribing information for additional clinically significant drug interactions.
Future Strategic Direction
Corey Fishman, Iterum’s Chief Executive Officer, stated, “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.”