Spero Therapeutics, Inc. announced that it received written agreement from the U.S. Food and Drug Administration (FDA), under a Special Protocol Assessment (SPA), on the design and size of PIVOT-PO, a pivotal Phase 3 clinical trial of tebipenem HBr in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP). PIVOT-PO is a global, randomized, double-blind, pivotal Phase 3 clinical trial of oral tebipenem H Br vs. IVimipenem cilastatin, in hospitalized adult patients with cUTI/AP.

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, which is consistent with FDA guidance for non-inferiority studies in cUTI/AP. 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.

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, which is consistent with FDA guidance for non-inferiority studies in cUTI/AP. The FDA has indicated that positive and persuasive results from PIVOT-PO, along with previously completed studies, could be sufficient to support approval of tebipenem HBr as a treatment for cUTI, including pyelonephritis, for a limited use indication.

Spero is also eligible to receive the following milestone/royalty payments under the terms of its license agreement with GSK, conditional upon achievement of certain progression of milestones: (1) up to an additional $120 million in development milestones as the Phase 3 clinical trial progresses; (2) up to $150 million in potential commercial milestones based on first commercial sales; (3) up to $225 million in potential sales-based milestones; and (4) low-single digit to low- double digit (if sales exceed $1 billion) tiered royalties on net product sales of tebipenem HBr in all territories, except Japan and certain other Asian countries.