Alembic Pharmaceuticals, Inc. has acquired UTILITY Therapeutics Ltd., a biotechnology company focused on developing PIVYA (pivmecillinam 185 mg tablets), marking a significant milestone in addressing the critical shortage of effective treatments for uncomplicated urinary tract infections (uUTI) in women.
Historic FDA Approval Addresses Treatment Gap
PIVYA represents the first antibiotic to earn FDA approval for uUTI in approximately 20 years, receiving regulatory clearance in April 2024. The penicillin-class antibacterial is indicated for female patients 18 years of age and older with uUTI caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus.
"With current therapies failing and the armament of uUTI antibiotics perilously thin, PIVYA provides U.S. clinicians with a new and effective treatment option that has a long safety record," said Tom Hadley, President and CEO of UTILITY therapeutics.
Novel Mechanism of Action
PIVYA features a unique mechanism of action that targets the cell wall of gram-negative bacteria. As an oral prodrug of mecillinam, it demonstrates in vitro activity against Enterobacterales in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBL) of the CTX-M, SHV, TEM, and AmpC groups. The inhibitory action of mecillinam on PBP-2 results in low cross-resistance with certain beta-lactams, with resistance frequency in E. coli ranging from 8×10⁻⁸ to 2×10⁻⁵ when exposed to 32-256 times MIC.
Clinical Trial Evidence
PIVYA demonstrated safety and efficacy in three controlled clinical trials. The most common adverse reactions occurring in ≥1% of patients included nausea (4.3%), diarrhea (2.1%), vulvovaginal candidiasis (1.8%), genital pruritus (1.8%), and headache (1.4%).
The trials compared different PIVYA dosing regimens to placebo, another oral antibacterial drug, or ibuprofen. Efficacy was assessed in the Microbiological Intent-to-Treat (micro-ITT) population, which included all randomized subjects with a positive baseline urine culture defined as ≥10⁵ colony-forming-units (CFU)/mL of a uropathogen.
Strategic Commercial Launch
Craig Salmon, President of Alembic Pharmaceuticals, Inc., emphasized the acquisition's strategic importance: "The acquisition of UTILITY and the commercialization of PIVYA are important steps in Alembic's strategic goal to provide branded pharmaceutical products to the U.S. healthcare market." The company plans to make PIVYA available in the U.S. in the fourth quarter of 2025.
Clinical Positioning and Impact
Dr. Morten Sommer, Professor of microbiology at the Technical University of Denmark and co-founder of UTILITY therapeutics, highlighted PIVYA's potential clinical impact: "With a novel mechanism of action, not previously deployed in the U.S., PIVYA can become a cornerstone of the treatment of urinary tract infections based on its first-line positioning in the Infectious Disease Society of America treatment guidelines."
Safety Profile and Contraindications
PIVYA carries specific contraindications including serious hypersensitivity reactions to beta-lactam antibacterial drugs, primary or secondary carnitine deficiency from inherited metabolic disorders, and acute porphyria. Healthcare providers must monitor for hypersensitivity reactions, severe cutaneous adverse reactions, carnitine depletion, and Clostridioides difficile-associated diarrhea.
Future Development Pipeline
UTILITY therapeutics holds exclusive U.S. commercial rights to two European-approved antibiotics, pivmecillinam and mecillinam. The intravenous formulation of mecillinam may be developed as a first-line therapy for complicated UTI in hospital settings, potentially expanding treatment options across the UTI spectrum.
The acquisition was supported by various stakeholders including the AMR Action Fund, reflecting the broader healthcare community's recognition of the urgent need for new antimicrobial treatments in an era of increasing antibiotic resistance.
