Presented at ESCMID Global 2026
Alireza Shamaei-Tousi1, Moritz Marquardt1, David R. Cameron1, Luis de la Fuente1, and Jutta Amersdorffer1
1Debiopharm International SA, Lausanne, Switzerland
Abstract
Background: Staphylococci are the leading pathogens in bone and joint infections (BJI), which remain clinically challenging due to high recurrence rates (~40%). Afabicin, a FabI inhibitor with microbiome-sparing properties, is in clinical development as a targeted anti-staphylococcal agent. Results from the first cohort of a Phase 2 BJI trial (2–3 weeks treatment) showed that afabicin achieved clinical response rates comparable to standard of care (SoC) in patients with BJI. These findings are further supported by results from the second cohort (3–6 weeks treatment) presented in this abstract.
Methods: This multicenter, open-label Phase 2 study evaluated the safety, tolerability, and efficacy of afabicin (55 mg IV / 80 mg PO, BID) versus predefined SoC therapies in participants with osteomyelitis, septic arthritis, or prosthetic joint infections. Investigators selected from SoC options which included IV cefazolin, vancomycin, linezolid, or clindamycin, and oral linezolid or clindamycin. SoC treatments were administered per approved regional labelling. In Cohort 2, participants were randomized (5:1) to receive treatment for 21–42 days.
Results: Twenty-six participants (22 afabicin, 4 SoC), with confirmed staphylococcal infection, were included in the microbiological intent-to-treat (mITT) population in Cohort 2. Median treatment duration was 40 days (afabicin) and 38 days (SoC). Osteomyelitis was the most common diagnosis (65%), and Staphylococcus aureus was the predominant pathogen (n=21; 18 methicillin-sensitive S. aureus). All participants were responders at Day 8. At end of treatment (EOT), 25/26 participants were responders (21/22 afabicin, 4/4 SoC). At 4 and 12 weeks post-EOT, 18/22 afabicin and all SoC participants were responders. No drug-related SAE was reported. Conclusions: Afabicin offers IV to oral switch option and demonstrated a favorable efficacy and safety profile in participants with staphylococcal BJI treated for 3–6 weeks. These findings support continued clinical development of afabicin for BJI indications.