Spero Therapeutics has ceased the development of its antibiotic candidate, SPR720, following disappointing results from a Phase IIa clinical trial. The trial, which investigated SPR720's efficacy in treating patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), failed to meet its primary endpoint, leading to the program's suspension and a significant reduction in the company's workforce.
The Phase IIa trial (NCT05496374) enrolled 25 patients with NTM-PD. An interim analysis of data from 16 patients revealed that SPR720 did not demonstrate a statistically significant difference in antimicrobial effect compared to placebo. The primary endpoint was the rate of change in log10 colony forming units per milliliter (CFU/mL). Additionally, potential dose-limiting safety issues, including three cases of Grade 3 hepatotoxicity, were observed in patients receiving the 1,000mg once-daily dose.
Spero Therapeutics noted that while SPR720 exhibited antimicrobial activity, the interim analysis did not show sufficient separation from the placebo group. The company intends to complete the data analysis for all 25 enrolled patients to determine the next steps for the SPR720 program, though further development seems unlikely.
Strategic Shift to Tebipenem HBr and SPR206
Faced with the setback, Spero Therapeutics plans to concentrate its resources on its other antibiotic programs, namely tebipenem HBr and SPR206. Tebipenem HBr, an oral carbapenem antibiotic, has been out-licensed to GSK, granting GSK global marketing rights, excluding certain Asian countries. Spero has already received $143.5 million from GSK as part of this partnership and is eligible for up to $400 million in additional milestone-based payments, along with tiered royalties on sales.
The Phase III PIVOT-PO trial (NCT06059846) is set to compare oral tebipenem HBr with intravenous imipenem and cilastatin in hospitalized adult patients with complicated urinary tract infections (cUTI). The study aims to enroll approximately 2,648 patients, with completion of enrollment expected in the second half of 2025.
SPR206, a next-generation polymyxin, is being evaluated as a potential treatment for multidrug-resistant (MDR) Gram-negative pathogens in patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). Spero has received FDA clearance to initiate a Phase II trial for SPR206; however, the trial's commencement is contingent on securing non-dilutive funding.
Financial Impact and Restructuring
In conjunction with the SPR720 program's suspension, Spero Therapeutics announced a workforce reduction of 39%. The company stated that these measures are intended to extend its cash reserves into mid-2026. Following the announcement, Spero's stock price experienced a decline of over 17% in premarket trading, reflecting investor concerns about the company's prospects.
The challenges faced by Spero Therapeutics mirror broader trends in antibiotic development, where clinical and regulatory hurdles often lead to program discontinuations and strategic realignments. Other companies, such as AN2 Therapeutics, have also recently suspended antibiotic development programs after disappointing trial results.
