Spero Therapeutics Halts SPR720 Development After Phase 2a Trial Fails to Meet Primary Endpoint
核心洞察
Spero Therapeutics suspends SPR720 development for NTM-PD (搜索) after Phase 2a trial fails to demonstrate sufficient separation from placebo in interim analysis.
The Phase 2a trial showed antimicrobial activity but raised safety concerns, including reversible grade 3 hepatotoxicity at the 1,000mg dose.
Spero will restructure operations, reducing workforce by 39% to extend cash runway into mid-2026 and focus on tebipenem HBr (搜索) and SPR206.
Spero Therapeutics has announced the suspension of its SPR720 development program following the interim analysis of a Phase 2a proof-of-concept study for the treatment of Nontuberculous Mycobacterial Pulmonary Disease (搜索) (NTM-PD (搜索)). The study, which enrolled 25 non-refractory patients, did not meet its primary endpoint of demonstrating a significant difference from placebo in the rate of change in log10 colony forming units per milliliter (CFU/mL).
Phase 2a Trial Results and Safety Concerns
The interim analysis, based on data from 16 patients, indicated that while SPR720 exhibited antimicrobial activity, it did not show sufficient separation from placebo. Furthermore, the analysis of the full 25-patient safety data revealed potential dose-limiting safety issues, including three cases of reversible grade 3 hepatotoxicity in patients dosed at 1,000 mg orally once daily. Given these findings, Spero has decided to suspend the current development program for SPR720 and will evaluate alternative paths forward after further data analysis.
Restructuring and Prioritization of Other Programs
As a result of the SPR720 program suspension, Spero Therapeutics will undergo a restructuring, including a reduction in workforce of approximately 39%. This restructuring aims to extend the company's cash runway into mid-2026 and support the advancement of its other key programs, including tebipenem HBr (搜索) and SPR206. Spero's unaudited cash balance at the end of Q3 2024 was $76.3 million.
Sath Shukla, Spero’s President and Chief Executive Officer, stated, "While a planned interim analysis provided evidence of antimicrobial activity, the trial unfortunately did not meet the primary endpoint. We are therefore suspending development of the SPR720 program and making adjustments to our organization accordingly."
Tebipenem HBr and SPR206 Development
Spero Therapeutics remains focused on advancing tebipenem HBr (搜索), an investigational oral carbapenem antibiotic, in the ongoing global Phase 3 PIVOT-PO clinical trial for complicated urinary tract infections (搜索) (cUTI (搜索)), including acute pyelonephritis (搜索) (AP (搜索)). The trial compares oral tebipenem HBr with intravenous imipenem cilastatin in hospitalized adult patients, with a target enrollment of approximately 2,648 patients and enrollment completion expected in the second half of 2025.
SPR206, an investigational, intravenously administered next-generation polymyxin, is also a priority for Spero. It has shown antibiotic activity against multidrug-resistant Gram-negative pathogens in preclinical studies. The FDA has cleared Spero's IND for a Phase 2 trial of SPR206 in patients with hospital-acquired or ventilator-associated bacterial pneumonia (搜索) (HABP/VABP (搜索)), contingent on the availability of non-dilutive funding.
About Spero Therapeutics
Spero Therapeutics is a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and multi-drug resistant bacterial infections. The company's pipeline includes tebipenem HBr (搜索) for cUTI (搜索) and SPR206 for MDR Gram-negative infections.