We are developing Tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) as an oral antibiotic for the treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) to help patients avoid hospitalizations (stay at home) and/or transition patients home after IV therapy (get home).
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. Carbapenems have emerged as the standard-of-care for many multidrug-resistant (MDR) Gram-negative bacterial infections, but today they are only available as intravenous therapeutics for such indications.
On April 6, 2022, Spero Therapeutics announced publication in the New England Journal of Medicine (NEJM) the results from the Phase 3 ADAPT-PO clinical trial for its investigational oral carbapenem antibiotic, tebipenem pivoxil hydrobromide (tebipenem HBr) in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP).
In June 2022, the FDA communicated that it had completed its review of the NDA and determined that the NDA could not be approved in its present form. In late June 2022, the FDA issued a Complete Response Letter for the tebipenem HBr NDA, where the FDA concluded that Spero’s Phase 3 cUTI clinical trial of tebipenem HBr (ADAPT-PO) was insufficient to support approval and that additional clinical study would be required. Spero then requested and completed a Type A meeting in August 2022 with the FDA, discussing the regulatory pathway forward for potential approval of tebipenem HBr. The Type A meeting minutes were received with proposed regulatory guidance regarding additional clinical study. The agency indicated that positive results from a single additional Phase 3 clinical trial supported by confirmatory nonclinical evidence of efficacy could be sufficient to support the approval of tebipenem HBr for the treatment of cUTI, including pyelonephritis for a limited use indication. With plans to advance additional Phase 3 clinical development and eventual commercialization, Spero entered into an exclusive license agreement with GSK for tebipenem HBr in September 2022. Pursuant to the license agreement, Spero received a $66 million upfront payment from GSK, and is eligible to receive up to $525 million in development, sales, and commercial milestones payments, as well as low single-digit to low double-digit tiered royalties on net product sales. In exchange, GSK was granted an exclusive license to develop and commercialize tebipenem pivoxil and tebipenem HBr in all territories, except Japan and certain other Asian countries, territories which were retained by Spero partner Meiji Seika. Per the license agreement, Spero is responsible for the execution and costs of a follow-up Phase 3 clinical trial of tebipenem HBr. GSK is responsible for the execution and costs of additional development, including Phase 3 regulatory filings and commercialization activities for tebipenem pivoxil and tebipenem HBr outside of the Meiji Seika territories.
In July, 2023, Spero 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. 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. Enrollment for PIVOT-PO is expected to begin in Q4 2023.
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Patients can follow the progress of SPR720 as the candidate moves through clinical trials. ClinicalTrials.gov is a database of clinical studies conducted worldwide.
(Blog post authored by Ankit Mahadevia)