Spero Therapeutics' Tebipenem HBr Phase 3 Trial Enrollment on Track; SPR720 Development Suspended
Key Insights
Spero Therapeutics' Phase 3 PIVOT-PO trial of tebipenem HBr (search) for complicated urinary tract infections (search) remains on track, with enrollment expected to complete in the second half of 2025.
The company has suspended development of SPR720 for nontuberculous mycobacterial pulmonary disease (search) after interim analysis showed insufficient separation from placebo.
Spero's SPR206 program, targeting multi-drug resistant Gram-negative pathogens (search), is ready for Phase 2 trials, contingent on securing non-dilutive funding.
Spero Therapeutics, a biopharmaceutical company focused on novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, announced its third-quarter 2024 operating results and provided a business update on November 14, 2024. The Phase 3 PIVOT-PO trial of tebipenem HBr (search) for complicated urinary tract infections (search) (cUTI) is progressing as planned, while the development of SPR720 has been suspended.
Tebipenem HBr Phase 3 Trial Update
The global Phase 3 clinical trial, PIVOT-PO, evaluating tebipenem HBr (search) for cUTI, including acute pyelonephritis (AP), is on track to complete enrollment in the second half of 2025. This randomized, double-blinded trial compares oral tebipenem HBr with intravenous imipenem cilastatin in hospitalized adult patients. The primary endpoint is the overall response, a combination of clinical cure and favorable microbiological response, assessed at the Test-of-Cure (TOC) visit. The trial aims to enroll approximately 2,648 patients. Tebipenem HBr is an investigational oral carbapenem antibiotic. Spero has granted GSK an exclusive license to commercialize tebipenem HBr in all territories except certain Asian territories.
SPR206 Program Advancement
Spero Therapeutics is also advancing its SPR206 program, an investigational, intravenously administered next-generation polymyxin. Preclinical studies have demonstrated antibiotic activity against MDR Gram-negative pathogens (search), including carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. The U.S. Food and Drug Administration (FDA) has cleared the company's IND for a Phase 2 trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The initiation of this trial is contingent on the availability of non-dilutive funding.
SPR720 Development Suspended
In October 2024, Spero Therapeutics suspended its development program for SPR720 following a planned interim analysis of the Phase 2a proof-of-concept study for nontuberculous mycobacterial pulmonary disease (search) (NTM-PD). The interim analysis revealed that the study did not meet its primary endpoint, showing insufficient separation from placebo, and highlighted potential dose-limiting safety issues, including three cases of reversible grade 3 hepatotoxicity in patients dosed at 1,000 mg orally once daily. SPR720 is an investigational oral prodrug that is converted in vivo to SPR719, targeting the ATPase site of DNA gyrase B (search) in mycobacteria. The company is currently evaluating other potential paths forward as the remaining data are collected and analyzed.
Financial and Corporate Updates
Following the suspension of the SPR720 development plans, Spero Therapeutics underwent a restructuring and reduction in force of approximately 39% in October 2024. This action is projected to extend the company's cash runway into mid-2026. Spero reported a net loss of $17.1 million, or ($0.32) per share, for the third quarter ended September 30, 2024, compared to a net loss of $3.2 million, or ($0.06) per share, for the same period in 2023. The company's cash and cash equivalents totaled $76.3 million as of September 30, 2024. Spero anticipates that its existing cash, along with expected milestone payments from GSK and other non-dilutive funding, will be sufficient to fund operating expenses and capital expenditures into mid-2026.
Sath Shukla, President and Chief Executive Officer of Spero, stated, "Enrollment in the Phase 3 tebipenem HBr (search) trial is progressing well, and we are on track to complete enrollment in the second half of 2025. Further, our work on the Phase 2 ready SPR206 program continues, contingent on availability of non-dilutive funding."