New UTI Solution: Orlynvah Wins FDA Approval

Orlynvah Approval For Uncomplicated Urinary Tract Infections (uUTIs)  

On October 25, 2024, the U.S. Food and Drug Administration (FDA) announced approval for a new drug called Orlynvah™ manufactured by Dublin-based Iterum Therapeutics plc. This new antibiotic treatment offers a potential solution for difficult-to-treat uncomplicated UTIs in appropriate patients.

Orlynvah (sulopenem etzadroxil and probenecid) is the first oral penem antibiotic approved for the treatment of uncomplicated urinary tract infections (uUTIs). It is also the first FDA-approved product in decades in an underserved uUTI market.

Orlynvah vs Other Approved Oral Agents

Orlynvah has a specific and first approved indication to treat uncomplicated urinary tract infections (uUTIs) caused by specific bacteria (Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis) in adult women who have limited or no other alternative options for oral antibiotic treatment (difficult-to-treat UTIs that do not respond to usually prescribed antibiotics).

Typical Antibiotics for the Treatment of Uncomplicated UTIs

An uncomplicated urinary tract infection (uUTI) or a simple UTI is a bacterial infection of the bladder or lower urinary tract in a patient with no structural abnormalities of the urinary tract and no other medical conditions such as diabetes. 

In contrast, a complicated UTI occurs in an individual with an abnormal urinary tract or other underlying health conditions, making it more challenging to treat this type of UTI. 

Antibiotics are the first line of treatment for urinary tract infections. The choice of antibiotic and the duration of antibiotic treatment depends on the type of bacteria found in your urine culture. 

According to the IDSA (Infectious Diseases Society of America), the following commonly approved oral agents are recommended as first-line treatment of uncomplicated UTIs: 

• Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS)

  • Dosage: 160/800mg twice daily for 3 days

• Nitrofurantoin (Macrobid, Macrodantin, Furadantin)

  • Dosage: 100mg twice daily for 5 days

• Fosfomycin (Monurol)

  • Dosage: 3g as a single dose

• Amoxicillin/clavulanate (Augmentin), cephalexin (Keflex), cefdinir (Omnicef)

• Ciprofloxacin (Cipro), levofloxacin (Levaquin) 

Short courses of antibiotic therapy are usually effective in treating simple UTIs. However, with antimicrobial resistance continuing to be a global health threat, UTIs caused by common bacteria such as E. coli are no longer susceptible to commonly prescribed antibiotics.

In other words, antimicrobial resistance occurs when microbes (bacteria, fungi, viruses) mutate, thus becoming resistant to antimicrobial agents designed to kill them. As a result, there is a need to develop new treatments and reevaluate antibiotic treatment protocols to emphasize on appropriate utilization of antibiotics. 

Learn how to get rid of a UTI fast.

Potential Impact on the Treatment Landscape For UTIs

Uncomplicated UTIs are one of the common infections affecting women. Approximately 50% of all women experience at least one uUTI in their life. This common infection results in approximately 10.5 million doctor visits with an estimated cost of $3.5 million per year in the U.S. alone.

The introduction of novel products like Orlynvah (sulopenem etzadroxil and probenecid), the first oral penem approved by the FDA for uncomplicated urinary tract infections, will bridge the treatment gap for uncomplicated UTIs caused by resistant bacteria. 

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Clinical Trials Results

Overview of Pivotal Phase III Clinical Trials: SURE 1 and REASSURE 

The safety and effectiveness of Orlynvah (oral sulopenem etzadroxil and probenecid) was evaluated in two phase 3 controlled, randomized, double-blind clinical trials. These clinical trials enrolled adult women with uncomplicated UTIs who received Orlynvah one tablet twice a day for 5 days. The clinical trials compared the effectiveness of Orlynvah to ciprofloxacin (SURE 1) and Augmentin (REASSURE) in adult women with uUTIs. 

Summary of Clinical Trial Results Supporting FDA Approval  

SURE 1 showed superiority of Orlynvah over ciprofloxacin in fluoroquinolone-resistant infections. Orlynvah had a composite response rate (combined clinical response and microbiological response rate) of 48% compared to 33% in the ciprofloxacin group.

REASSURE showed non-inferiority and statistical superiority of Orlynvah to Augmentin (amoxicillin/clavulanate) in the Augmentin-susceptible population. The composite response rate for Orlynvah was 62% compared to 55% in the Augmentin (amoxicillin/clavulanate) group. 

Orlynvah was not found to be effective in clinical trials evaluating this antimicrobial therapy in patients with complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs).

Efficacy in Treating Specific Strains: Escherichia Coli, Klebsiella Pneumoniae, Proteus Mirabilis  

Orlynvah contains two active ingredients:

• Sulopenem etzadroxil, an oral penem antibiotic, 500 milligrams (mg)

• Probenecid, a renal tubular transport inhibitor, 500 mg

Oral sulopenem is active against Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis that are common causes of UTIs. Probenecid prevents elimination of sulopenem by the kidneys and helps to keep the antibiotic in the body longer.

Implications For Healthcare Professionals  

Considerations for Prescribing Orlynvah  

Orlynvah is approved to treat uncomplicated urinary tract infections caused by specific microorganisms (Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis) in adult women with limited or no alternative treatment options. 

Novel products like Orlynvah can serve as an alternative oral antimicrobial in treating fluoroquinolone-resistant infections. 

Implications for Antibiotic Stewardship and Avoiding Off-Label Use

Empiric use of antibiotics (starting antibiotic treatment for a UTI before the causative bacteria and its antibiotic susceptibility have been identified) is widespread because of the convenience. However, it can potentially contribute to the development of antimicrobial resistance. 

Antimicrobial stewardship refers to the use of antibiotics in a way that maximizes therapeutic effect while limiting the development of antibiotic resistance. 

Appropriate antibiotic use consists of using the narrowest-spectrum antibiotic possible and avoiding widespread empiric use of broad-spectrum antimicrobial agents. 

Recommendations For Patient Populations With Limited Treatment Options  

Orlynvah is specifically approved for uncomplicated UTIs in adult women caused by three specific bacteria. Healthcare providers should avoid off-label use of this antimicrobial therapy for other types of UTIs as part of antimicrobial stewardship.

Orlynvah Oral Penem Pros & Cons 

Pros

• Orlynvah has become the first oral penem approved in the U.S. market, allowing an excellent alternative in the community setting.

• Clinical trials have demonstrated that Orlynvah is statistically superior to existing treatments.

• There are limited treatment options for uncomplicated UTIs. Orlynvah serves an underserved uUTI market. 

Cons

• Orlynvah has a limited scope of use. It is only approved for use in adult women with uncomplicated UTIs who have limited or no other treatment options.

• Orlynvah is only approved to treat UTIs caused by designated microorganisms (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis).

Patient Perspectives on Orlynvah  

Potential Benefits: The Breakthrough In Antibiotic Treatments For uUTIs In Women  

Orlynvah is the first FDA-approved therapy for uUTIs in adult women with limited treatment options. It offers an excellent alternative treatment option to patients suffering from uncomplicated UTIs. Orlynvah has shown superiority to other oral agents and offers a way to combat antimicrobial resistance. Orlynvah, therefore, offers hope for patients suffering from difficult-to-treat uUTIs that are not treatable with alternative oral antibacterial treatments. 

Side Effects of Orlynvah

The most common adverse reactions reported in patients treated with Orlynvah are headache, nausea, diarrhea, vomiting, and fungal infections of the vulva and vagina.

More serious side effects include hypersensitivity reactions, Clostridium-difficile-associated diarrhea (CDAD), and worsening gout.

Availability and Accessibility

Orlynvah will be available by prescription to adult women with uncomplicated urinary tract infections caused by susceptible microorganisms and with limited or no other treatment options. Orlynvah is a brand name drug and a lower-cost generic is not currently available. 

Summary of Orlynvah’s Approval and Its Importance  

Orlynvah is the first oral penem FDA-approved therapy in the U.S. for use in appropriate patients. The approval of Orlynvah is important because it is only the second FDA-approved treatment for uncomplicated urinary tract infections (uUTIs) in the past two decades. Pivya (pivmecillinam) was approved by the FDA to treat uncomplicated UTIs in female adults in April 2024. 

Other New and Ongoing Developments In UTI Treatments  

In 2024, after two decades, the FDA approved pivmecillinam (Pivya), a new antibiotic to treat urinary tract infections (UTIs) in women. Pivmecillinam is an oral penicillin antibiotic that has been prescribed in Europe for 40 years for uncomplicated urinary tract infections, but it has only recently been approved in the U.S.

Other novel drugs that are being developed for UTIs include cephalosporins such as cefiderocol and combinations of beta-lactam antibiotics with cephalosporins and carbapenems to treat Gram-negative UTIs.