Spero Therapeutics, Inc. announced the first patient, first visit for PIVOT-PO, a global pivotal Phase 3 clinical trial of tebipenem HBr in patients with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). Spero is entitled to receive $95 million in development milestone payments from GSK, which is payable in four equal installments over two years. PIVOT-PO is a global, randomized, double-blind, pivotal Phase 3 clinical trial of oral tebipenem HBr vs.

IV imipenem cilastatin, in hospitalized adult patients with cUTI/AP. Patients are being randomized 1:1 to receive tebipenem HBr (600 mg) orally every six hours, or imipenem cilastatin (500 mg) IV every six hours, for a total of seven to ten days. The primary efficacy endpoint will be overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit.

The primary analysis for the trial will be an assessment of non-inferiority (NI) in the microbiological intention-to-treat population, based on a 10% NI margin. The trial is designed to enroll approximately 2,648 patients, with randomization stratified by age, baseline diagnosis (cUTI or AP), and the presence or absence of urinary tract instrumentation. For further details on the trial, refer to clinicaltrials.gov identifier NCT06059846.

The FDA has indicated that positive and persuasive results from PIVOT-PO, supported with confirmatory evidence of efficacy, could be sufficient to support approval of tebipenem HBr as a treatment for cUTI, including pyelonephritis, for a limited use indication. Under the terms of its license agreement with GSK, Spero is also eligible to receive the following milestone/royalty payments: (1) an additional $25 million in development milestones; (2) up to $150 million in potential commercial milestones based on first commercial sale; (3) up to $225 million in potential sales-based milestones; and (4) low-single digit to low-double digit tiered royalties on net product sales of tebipenem HBr in all territories, except Japan and certain other Asian countries. Tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) is Spero?s novel late-stage development asset, an oral formulation of tebipenem pivoxil, a carbapenem antibiotic of the ß-lactam class marketed by Meiji Seika Pharma Co.

Ltd. (Meiji) in Japan as Orapenem® since 2009 for pediatric infections limited to pneumonia, otitis media and sinusitis. Carbapenems are an important subclass of antibiotics because they have been observed to be safe and effective in the treatment of drug-resistant Gram-negative bacterial infections. Tebipenem HBr is being developed for the treatment of complicated urinary tract infections, including AP, caused by certain microorganisms. If approved, tebipenem HBr may be the first oral carbapenem antimicrobial to receive marketing approval in the United States.

Tebipenem HBr has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the US Food and Drug Administration (FDA) for the treatment of cUTI and AP. Tebipenem HBr Research Support: Select tebipenem HBr studies have been funded in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C.