For the first time in more than 20 years, the FDA has approved a treatment for uncomplicated urinary tract infections (uUTI). And the nod has come for an oral antibiotic that has been available in Europe for more than 40 years.
It’s an odd set of circumstances and a dose of foresight by Utility Therapeutics that bring Pivya (pivmecillinam) to the market in the United States in the therapy’s golden years. The London-based company was formed specifically to develop and commercialize pivmecillinam in the U.S. where antimicrobial resistance is growing to standard of care antibiotics.
The decreased “utility” of first-line antibiotics and the void the company is attempting to fill in the U.S. were the inspiration of the name of the company. And the void is significant as more than 30 million uUTIs are diagnosed every year in the U.S., with nearly half of all women contracting the infection at some point in their life. Outside of hospital setting, UTIs account for more antibiotic use than any other disorder.
In 2018, Utility inked a licensing agreement with LEO Pharma, acquiring the U.S. rights to pivmecillinam and its subcutaneous formulation mecillinam, which the company has submitted for approval as a first-line therapy for complicated urinary tract infections (cUTI) in the hospital setting. The difference between cUTIs and uUTIs is that the former has reached the kidneys while the latter is limited to the bladder.
“The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective and Pivya will provide an additional treatment option for uncomplicated UTIs,” Peter Kim, M.D., the director of the Division of Anti-Infectives at the FDA’s Center for Drug Evaluation and Research, said in a release.
The year that Utility acquired the rights to pivmecillinam and mecillinam, the FDA signed off on each as a Qualified Infectious Disease Product (QIDP). The status is extended to antibacterial and antifungal drug candidates intended to treat serious or life-threatening infections. When a QIDP treatment is approved, it gains an additional five years of market exclusivity.
On the same day in January, when Utility revealed that the FDA had accepted the company’s new drug applications for pivmecillinam and mecillinam, it also announced it had received private funding from the AMR Action Fund. The global initiative—which was established by several prominent drugmakers including Amgen, Bayer, Eli Lilly, GSK, Novo Nordisk and Roche—invests in the development of new antimicrobial therapeutics.
In addition to being a prodrug, which means that it is not pharmacologically active until it is digested and absorbed into the system, Pivya has a unique mechanism of action, targeting penicillin binding protein-2 in the cell wall of gram-negative bacteria.
Pivya’s efficacy was assessed in separate trials versus placebo, an oral antibacterial and ibuprofen. The primary measure of efficacy in the studies was the composite response rate, which included clinical cure (resolution of the symptoms of the uUTI that were present in patients at trial entry and no new symptoms) and microbiological response (demonstration that the bacteria cultured from patients’ urine at trial entry was reduced).
In the placebo trial, 62% of the participants who received Pivya achieved composite response compared to 10% of those on placebo. In the oral antibacterial trial, 72% of the subjects who received Pivya achieved composite response versus 76% of those on the comparator. In the third trial, 66% of the subjects who received Pivya achieved composite response compared to 22% of those on ibuprofen.
Commonly prescribed drugs for uUTIs in the U.S. are bactrim (sulphamethoxazole/trimethoprim), nitrofuranatoin and fluoroquinolones. But more than 1 in 5 who receive these are resistant, which can lead to progression of the disease, including life-threatening sepsis.
Last month, Germany’s Allecra Therapeutics scored FDA approval for its antibiotic Exblifep, which is a combination of cephalosporin antibacterial cefepime and the beta-lactamase inhibitor enmetazobactam, to treat cUTI. The approval came days after the U.S. regulator rejected another combo therapy in the same indication from Venatorx Pharmaceuticals and Melinta Therapeutics.