Iterum Therapeutics US FDA Approval
On October 25, 2024, Iterum Therapeutics (ITRM) announced that the U.S. FDA has approved Iterum’s new drug application for ORLYNVAH™ (sulopenem, etzadroxil, and probenecid) for the treatment of the uncomplicated urinary tract infections (uUTIs) caused by the designated microorganisms Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women who have limited or no alternative oral antibacterial treatment options. This is the first approved indication for ORLYNVAH™ and the first FDA-approved product for Iterum.From Iterum Therapeutics
Corey Fishman, Iterum’s Chief Executive Officer said, “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. As the first oral penem approved in the U.S., 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™ to maximize value for our stakeholders.” The FDA approval of ORLYNVAH™ was based on a clinical development program supported by a robust data package, including two pivotal, Phase 3 clinical trials (known as SURE 1 and REASSURE) that evaluated the safety and efficacy of ORLYNVAH™ compared to ciprofloxacin (SURE 1) and Augmentin™ (REASSURE) in the treatment of adult women with uUTI. SURE 1 showed superiority to ciprofloxacin in fluoroquinolone-resistant infections, while REASSURE showed non-inferiority and statistical superiority to Augmentin™ in the Augmentin™ susceptible population. ORLYNVAH™ was generally well tolerated in both SURE 1 and REASSURE clinical trials.From Other Experts
Marjorie Golden, MD, FIDSA, Site Chief, Infectious Disease, St. Raphael Campus Yale New Haven Hospital said, “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.”Conference Call
Iterum hosted a conference call on Monday, October 28, 2024. A replay will be available in the Events & Presentations section of Iterum’s website following the call.About uUTI
UTIs are among the most common bacterial infections encountered in the community. UTIs are infections of the bladder occurring mainly in women. Up to 60% of women will have a uUTI in their lifetime. Up to 40% of women with a history of uUTI will have a recurrence of their infection. There are approximately 40 million uUTI prescriptions generated annually in the United States, and we estimate approximately 1% of those infections are caused by pathogens that are resistant to all commonly available classes of oral antibiotics. Rising antibiotic resistance, an aging population with comorbidities, and sub-optimal safety profiles of existing oral treatment options are making antibiotic selection more challenging for treating physicians.About ORLYNVAH™
ORLYNVAH™ is a novel oral penem antibiotic for the treatment of uUTI. ORLYNVAH™ possesses potent activity against species of Enterobacterales including those that encode extended spectrum beta-lactamase (ESBL) or AmpC-type beta-lactamases that confer resistance to third generation cephalosporins.Indications and Important Safety Information
Indications & Usage ORLYNVAH™ a combination of sulopenem etzadroxil, a penem antibacterial, and probenecid, a renal tubular transport inhibitor, is indicated for the treatment of uUTI caused by the designated microorganisms Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women who have limited or no alternative oral antibacterial treatment options. Limitations of Use ORLYNVAH™ is not indicated for the treatment of:- Complicated urinary tract infections (cUTI) or step-down treatment after intravenous antibacterial treatment of cUTI
- Complicated intra-abdominal infections (cIAI) or step-down treatment after intravenous antibacterial treatment of cIAI.
Important Safety information
Contraindications- Patients with a history of hypersensitivity to the components of ORLYNVAH™ (sulopenem etzadroxil and probenecid) or other beta-lactam antibacterial drugs.
- Patients with known blood dyscrasias.
- Patients with known uric acid kidney stones.
- Concomitant use of ORLYNVAH™ and ketorolac tromethamine is contraindicated.
- Hypersensitivity Reactions: Hypersensitivity reactions have been reported in patients treated with ORLYNVAH™.
- Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with beta-lactam antibacterial drugs.
- Severe allergic reactions and anaphylaxis have been reported with the use of probenecid (a component of ORLYNVAH™). If an allergic reaction to ORLYNVAH™ occurs, discontinue the drug and institute appropriate therapy.
- Clostridioides difficile-Associated Diarrhea (CDAD): This has been reported with nearly all systemic antibacterial agents. Evaluate if diarrhea occurs.
- Exacerbation of Gout: When prescribing ORLYNVAH™ to patients with a known history of gout, ensure appropriate therapy of gout is instituted
Adverse Reactions
The most common adverse reactions (≥2%) in patients treated with ORLYNVAH™ were diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting. Drug Interactions- Ketoprofen: Concomitant use is not recommended.
- There are no available data on ORLYNVAH™ use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
- There are no data on the presence of ORLYNVAH™ or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production.
- The safety and effectiveness of ORLYNVAH™ in pediatric patients have not been established.
- No dosage adjustment based on age is required. ORLYNVAH™ is known to be substantially excreted by the kidney, and geriatric patients are anticipated to have reduced renal function. Recommendations for use in elderly patients should be based on renal function.