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New Antibiotic Hits The Market To Tackle Stubborn UTIs

No doubt about it, UTIs suck. They burn, they itch, they come back just when you think you're in the clear. But for those dealing with these relentless infections, there's finally a new line of defense.

A new type of antibiotic is now available for some of the most annoying infections around. This month, the Food and Drug Administration approved Iterum Therapeutics' Orlynvah for certain kinds of urinary tract infections that aren't likely to respond to other drugs.

UTIs are some of the most common infections that people encounter, particularly women. About 60% of women in the U.S. Are estimated to experience at least one uncomplicated UTI (a UTI with no signs of structural damage or other health conditions) in their lifetime. While UTIs were once easily treatable with just about any simple course of antibiotics, many infections nowadays are resistant to at least one or more front-line drugs used against them. This added hardiness not only makes it harder to treat UTIs early before they cause more serious trouble, but also increases the risk of having recurrent UTIs. So scientists have been desperate to find newer antibiotics that can treat these resistant infections.

Orlynvah is the first drug of its kind. It contains a combination of sulopenem etzadroxil, which belongs to a subclass of antibacterials called penems, and probenecid, a renal tubular transport inhibitor that has been used in the past to boost the duration of antibiotics in our body. Penems are synthetic antibiotics that has shown great promise in treating a wide variety of commonly resistant germs, but Orlynvah is the first ever oral penem to be approved in the U.S.

The drug has been approved to treat certain uncomplicated UTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis bacteria. Importantly, Orlynvah is intended for people who have limited or no other alternative oral antibacterial options for their UTIs, such as infections that haven't responded to past treatment or infections that show clear resistance to other drugs through testing. The FDA approved Orlynvah on the basis of two Phase III trials, which found that it outperformed or matched the effectiveness of other standard antibiotics for uncomplicated UTIs, including resistant infections.

"The FDA approval of sulopenem 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, an infectious disease specialist at the St. Raphael Campus of Yale New Haven Hospital who was involved in the drug's clinical research, in a statement from Iterum. "Based on the totality of clinical data generated, sulopenem has the potential to be an important treatment alternative for use in the community."

As valuable as Orlynvah will be for doctors and patients, the drug isn't a cure-all for UTIs in general. The drug failed to pass clinical trials testing its effectiveness against complicated UTIs or complicated intra-abdominal infections. And like many newer antibacterial drugs, its use will be carefully managed to delay the emergence of bacterial strains that evolve resistance to it.

Still, Orlynvah should be able to prevent plenty of UTI-related misery. While these infections aren't always apparent, they can cause pelvic pain, frequent and/or burning urination, and even blood in urine. Left untreated, UTIs can also raise the risk of a more serious kidney infection, a narrowed urethra in men, and even sepsis (a life-threatening inflammation that can cause widespread organ damage).

FDA Approves New Antibiotic For Uncomplicated UTIs

The US Food and Drug Administration (FDA) approved a new oral antibiotic to treat uncomplicated urinary tract infections (uUTIs).

Orlynvah (sulopenem etzadroxil and probenecid) is a broad-spectrum oral penem antibiotic that's designed to treat UTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis bacteria in adult women who have limited or no alternative treatment options. Iterum Therapeutics created the drug.

The FDA said it approved the drug based partly on two phase 3 randomized controlled trials that compared Orlynvah to standard treatments for uUTIs. 

A trial on 2,214 adult women who had uUTI found that women on Orlynvah had a 62% composite response rate (combined microbiologic and clinical response) compared with a 55% composite response rate in patients treated with amoxicillin/clavulanate. In another trial on 1,660 adult women with uUTIs caused by ciprofloxacin-resistant pathogens, Orlynvah was superior to ciprofloxacin, with a 48% composite response rate compared with 33% in the ciprofloxacin group.

The most common side effects women experienced on Orlynvah were diarrhea, nausea, vaginal yeast infection, headache and vomiting. 

"Orlynvah offers new hope for patients suffering from difficult-to-treat uUTIs," Corey Fishman, Iterum Therapeutics' interim CEO, said in a company press release. "As the first oral penem approved in the US, Orlynvah offers an excellent alternative treatment option for appropriate patients in the underserved uUTI market."

At the FDA's Antimicrobial Drugs Advisory Committee on Sept. 10, committee members agreed that Orlynvah could be beneficial for some patients, but had concerns that off-label use could boost resistance to carbapenems, which are closely related to penems and an important class of antibiotics for serious, multidrug-resistant infections. 

"While an oral penem for treatment of resistant bacteria causing uUTI could potentially address an unmet need, its use in an ambulatory setting where treatment is most commonly empiric raises concern for inappropriate use which may contribute to AMR [antimicrobial resistance]," the agency said in a document.

Careful antimicrobial stewardship is "needed to ensure appropriate positioning of sulopenem etzadroxil/probenecid in the hierarchy of treatment options for uUTI."Orlynvah is the first oral penem approved in the US. The FDA's prescribing information states that Orlynvah should be used only to treat uUTI that are, or are thought to be, caused by susceptible bacteria. The drug wasn't approved as a primary or step-down treatment for complicated UTIs or for complicated intra-abdominal infections.

FDA OKs New Drug For Urinary Tract Infections

Oct. 28, 2024 –The FDA has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don't have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don't work well, often due to antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like E. Coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

"Orlynvah has the potential to be an important treatment option for those who need it," she said in a news release from Iterum Therapeutics, the drug's maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

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