Probenecid

Spero’s SPR729 is a prodrug that converts into an active form that targets ATPase site of DNA gyrase B in mycobacteria. Image credit: Lemonsoup14 / Shutterstock. Spero Therapeutics has suspended the development of its antibiotic SPR720, after the therapy failed to meet the primary endpoint in a Phase IIa trial in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). The company was quick to note that whilst SPR720 showed antimicrobial activity, “the interim analysis did not show sufficient separation from placebo.” Spero also noted that it plans to lay off 39% of its staff. Following the announcement, the company’s stock was down by over 17% in premarket trading today. Spero reported that it has enough cash reserves to fund operations into mid-2026. The Phase IIa trial (NCT05496374) enrolled 25 non-refractory patients with SPR720. The interim analysis of 16 patients showed no differentiation in antimicrobial effect from placebo evaluated using the rate of change in log10 colony forming units per millilitre (CFU/mL), the study’s primary endpoint. Potential dose-limiting “safety issues”, including three cases of Grade 3 hepatotoxicity, were seen in patients receiving 1,000mg orally once daily dose. Spero plans to complete the data analysis of all 25 enrolled patients and “determine the next steps for the SPR720 program over the next several months.” The company plans to funnel its resources into two of its antibiotic programmes – an oral carbapenem antibiotic, tebipenem HBr, and SPR206, a next-generation polymyxin. Spero has out licenced tebipenem HBr to GSK, with the latter having global marketing rights to the therapy, except in certain Asian countries. Spero has received $143.5m from GSK as part of the partnership to date and is eligible to receive up to $400m in additional milestone-based payments along with tiered royalties on sales. The Phase III PIVOT-PO trial (NCT06059846) will compare oral tebipenem HBr with the two carbapenem antibiotics combination, intravenous imipenem and cilastatin, in hospitalised adult patients with complicated urinary tract infections (cUTI). The study is expected to recruit about 2,648 patients with cUTI, with enrolment planned for completion in the second half of 2025. Antibiotic development has seen mixed results in recent months. Last week, the US FDA approved Iterum Therapeutics’s Orlynvah (sulopenem etzadroxil and probenecid) for treating uncomplicated UTIs (uUTIs) caused by E. coli, Klebsiella pneumoniae or Proteus mirabilis in adult women who have limited or no alternative antibacterial treatment options. Whilst AN2 Therapeutics suspended development for its lead antibiotic, epetraborole, after it failed to show efficacy in Phase II/III trial (NCT05327803). AN2 was evaluating epetraborole as a treatment for refractory mycobacterium avium complex (MAC) lung disease. Spero plans to evaluate SPR206 as a treatment for multidrug-resistant (MDR) gram-negative pathogens in patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The company has received clearance from the US Food and Drug Administration (FDA) to start a Phase II trial. However, Spero noted that trial initiation is “contingent on availability of non-dilutive funding.” Following the recent round of lay-offs, Spero joins the list of pharmaceutical companies such as Aerovate Therapeutics , Sage Therapeutics and Shattuck Labs that have fired workers in the l to funnelmoney into their clinical development pipelines.

iStock, hapabapa Orlynvah is the first oral penem approved in the U.S. and Iterum Therapeutics’ first FDA-approved product. CEO Corey Fishman said the company will renew its efforts to look for a potential partner to maximize value for its stakeholders. The FDA on Friday signed off on Iterum Therapeutics’ oral antibiotic sulopenem etzadroxil and probenecid, which will now be marketed as Orlynvah, for the treatment of uncomplicated urinary tract infections in adult women. Orlynvah, Iterum’s first FDA-approved product, is cleared for three designated microorganisms— Escherichia coli , Klebsiella pneumoniae and Proteus mirabilis —and is indicated for women with limited or no available alternative oral antibiotic options. Iterum CEO Corey Fishman in a statement called Orlynvah’s approval a “historic milestone” that “offers new hope for patients suffering from difficult-to-treat uUTIs (uncomplicated urinary tract infections).” Orlynvah is “the first oral penem approved in the U.S.,” Fishman said, noting it is “an important way to combat antimicrobial resistance to other approved oral agents and offers a potential solution to patients and physicians.” To bring Orlynvah to the market and boost its commercialization efforts, Iterum will “renew” its “efforts to achieve a strategic transaction involving Orlynvah with the goal of maximizing value for our stakeholders,” Fishman said. The FDA’s decision on Friday was backed by Iterum’s clinical data for Orlynvah, including two Phase III trials. In the pivotal late-stage REASSURE study, topline data which were released in January 2024 , the oral sulopenem showed statistical non-inferiority to Augmentin (amoxicillin/clavulanate) in terms of overall response. Orlynvah significantly outperformed Augmentin at overall treatment success. Safety outcomes were comparable between treatment groups. Iterum’s data package also included findings from the pivotal Phase III SURE 1 study, which in June 2020 showed that the oral sulopenem was better than ciprofloxacin in patients with quinolone-resistant infections. SURE 1 also found Orlynvah to be safe, with adverse events developing at a comparable frequency as in the ciprofloxacin-treated group. Iterum filed a New Drug Application to the FDA but failed to secure approval. In July 2021, the regulator handed the Dublin, Ireland-based biotech a Complete Response Letter, noting that while SURE 1 had established that oral sulopenem was superior than ciprofloxacin, Iterum would need to run an additional trial that uses a different comparator drug. Iterum filed its resubmission earlier this year, after which the FDA convened its Antimicrobial Drugs Advisory Committee. The panel was not asked to vote on the approvability of Orlynvah, but Fishman said in a statement after the meeting that the company was “encouraged” by the discussion, “which acknowledged oral sulopenem as an important treatment option for certain patients with uUTI.”