afabicin (Debio 1450)
Selective antibiotic against severe Staphylococcus infections
afabicin (Debio 1450), is the first-in class of a novel antibiotic class, fabiotics, that inhibits fatty acid synthesis in staphylococci by targeting the Fabl enzyme. It fulfills all four WHO 2020 innovativeness criteria, i.e. new chemical class, new target, new mode of action and no cross-resistance to other antibiotic classes. As a result of its potent selective activity, afabicin specifically targets staphylococci while preserving intestinal microbiota. The compound currently is in phase II research for the treatment of Bone and Joint infections (BJI) due to staphylococci. The compound is also being researched in staphylococcal acute bacterial skin and skin structure infections (ABSSSI).
Product Snapshot
FabI Inhibitor
Inhibition of bacterial fatty acid synthesis
Being researched in:
- Bone and Joint infections
- ABSSSI
In short
Afabicin offers a unique anti-stapylococcal mechanism of action with a narrow spectrum of activity, providing a promising investigative therapy for the treatment for hard-to-treat staphylococci infections
Highly potent first-in-class fabI inhibitor, in both oral and intravenous (IV) formulations currently in phase II clinical research in the treatment of BJI
Focus on Bone and Joint Infections
Highly associated with Staphylococci bacteria
Bone and joint infections are a group of diseases that include osteomyelitis, septic arthritis and prosthetic joint infections affecting over 30,000 people per year within the US, UK, France, Germany, Spain and Italy combined. These conditions are associated with significant morbidity and, in certain circumstances, mortality worldwide. Staphylococci are the most common bacteria, identified in 30 to 70% of the cases.
Clinical trials
ABSSSI
Phase II, randomized, non-inferioritystudy
A phase II study was conducted in patients with staphylococcal Acute Bacterial Skin and Skin Structure Infections (ABSSSI) demonstrating the efficacy and safety of this first-in-class staphylococcal-selective antibiotic afabicin with the two doses tested vs. active comparator vancomycin / oral linezolid . The study objectives were met, demonstrating non-inferiority of Debio 1450 to comparator in all pathogenic staphylococci species infected patient populations including MRSA and ensuring that treatment with Debio 1450 at both doses was safe and well tolerated.
Mode of action: FabI Inhibitor
Inhibition of bacterial fatty acid synthesis
The active moiety of afabicin inhibits the fatty acid synthesis (FASII) pathway in staphylococci bacteria by targeting FabI. FabI, an enoyl-acyl carrier protein (ACP) reductase, catalyzes the final step in the fatty acid chain elongation by reducing enoyl-ACP to acyl-ACP. The FabI enzyme is essential for bacterial growth and survival and it is highly conserved across all staphylococcal species. By inhibiting FabI, FabI Inhibitor represent a novel antibacterial class that has the potential to address challenges of bacterial resistance.