Sulfamethoxazole/Trimethoprim

Nearly half of women will get a urinary tract infection in their lifetime. For the first time in more than 20 years the FDA has approved an antibiotic to treat the condition. 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.

ELIMINATE trial is evaluating LBP-EC01 for treating urinary tract infections caused by drug-resistant E. coli Funding to support advancement into Part 2 of ELIMINATE trial RESEARCH TRIANGLE PARK, N.C., Jan. 23, 2024 (GLOBE NEWSWIRE) -- Locus Biosciences Inc. (“Locus”), a clinical-stage biotechnology company developing a new class of precision engineered bacteriophage treatments for a diverse set of bacterial diseases, today announced the release of $23.9 million from the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, to continue the development of Locus’ CRISPR-enhanced bacteriophage therapy, LBP-EC01, for treating urinary tract infections (UTIs) caused by drug-resistant Escherichia coli (E. coli) based on positive results from a Phase 2a clinical trial. Worldwide, an estimated 150 million people are affected by UTIs each year. Approximately 80% of these are caused by E. coli, often including difficult-to-treat strains that are resistant to commonly used antibiotics. Up to 40% of UTI patients experience a recurrence, often within months of the first episode. Both the U.S. Centers for Disease Control and Prevention and the World Health Organization have identified antibiotic-resistant E. coli as an urgent and serious public health threat requiring development of new treatments. “Engineered bacteriophage have emerged as one of the most promising technologies for addressing the worldwide public health crisis of multi-drug resistant (MDR) bacterial infections. While multiple small-scale studies have shown promise, the field urgently needs a definitive large-scale placebo-controlled study to conclusively test the efficacy of an engineered bacteriophage therapy,” said Paul Garofolo, Co-founder and CEO of Locus. “We are incredibly grateful for our partnership with BARDA in funding this clinical trial of a potential first-in-class precision medicine for an important unmet medical need.” The company’s recent successful completion of the uncontrolled open-label Part 1 portion of the two-part ELIMINATE Phase 2 trial triggered the release of this tranche of funding under its $85 million contract (75A50120C00169) with BARDA. The funding will be used to advance LBP-EC01 into the blinded, placebo-controlled, Part 2 of the ELIMINATE Phase 2 trial. In 2020, Locus and BARDA announced an agreement to co-fund development of LBP-EC01. Under the contract, BARDA will provide up to $85 million in funding to Locus as part of a $152 million program to support Phase 2 and Phase 3 clinical trials and other activities required to seek marketing approval from the U.S. Food and Drug Administration for LBP-EC01. The award announced today brings the amount released under the contract to $48.9 million. About the ELIMINATE Trial The two-part multicenter Phase 2 ELIMINATE trial is evaluating LBP-EC01 used concomitantly with trimethoprim/sulfamethoxazole (TMP/SMX) in adult female patients for the treatment of uncomplicated UTIs caused by drug resistant E. coli. The uncontrolled open-label Part 1 (dose-regimen selection) evaluated the safety, tolerability, pharmacokinetics and clinical and microbiologic outcomes of LBP-EC01 and TMP/SMX in 39 patients with uncomplicated UTI. Part 2 of the study has a primary objective of determining the efficacy of LBP-EC01 when used concomitantly with TMP/SMX, compared to control (placebo plus TMP/SMX), based on combined clinical and microbiological response of acute uUTI caused by drug resistant E. coli in up to 288 adult female patients. This project has been funded in whole or in part with federal funds from the Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract number 75A50120C00169. For more information, visit clinicaltrials.gov using the identifier NCT05488340. Patients interested in participating in Part 2 of the Phase 2 trial can visit . About LBP-EC01 LBP-EC01 is a CRISPR-enhanced bacteriophage therapy in development for the treatment of urinary tract infections and other infections caused by the bacterial pathogen Escherichia coli (E. coli). It is a bacteriophage cocktail engineered with a CRISPR-Cas3 construct targeting the E. coli genome. The precision medicine product works through a unique dual mechanism of action utilizing both the natural lytic activity of the bacteriophage along with the DNA-targeting activity of CRISPR. LBP-EC01 previously met all primary and secondary endpoints and demonstrated safety and tolerability in a Phase 1b trial. LBP-EC01 is currently being evaluated in a Phase 2 trial for the treatment of UTIs caused by E. coli. About Locus Biosciences Locus Biosciences is creating a new class of precision biotherapeutics with clinical-stage engineered bacteriophage treatments for a diverse set of bacterial and microbiome/inflammatory diseases. A world-leading bacteriophage discovery, synthetic biology, and manufacturing platform powers the company. Locus engineers bacteriophage - naturally occurring viruses that target bacteria - to kill pathogenic bacteria, while sparing good bacteria, through programmable precision anti-bacterials with CRISPR-Cas3 and other therapeutic payloads. Its artificial intelligence and machine-learning based discovery engine targets bacteria that are associated with disease across therapeutic areas including infectious disease, immunology, and oncology. Locus has secured multiple non-dilutive partnerships to support development of the company’s platform and programs. These include contracts with Biomedical Advanced Research and Development Authority (BARDA) for Locus’ lead asset targeting E. coli and Combatting Antibiotic Resistant Bacteria Accelerator (CARB-X) for Locus’ asset targeting K. pneumoniae. For more on the Research Triangle Park, N.C.-based company, visit . Media Contact: Heather Anderson 6 Degrees handerson@6degreespr.com