Early-Stage Antibiotic for Bone and Joint Infections Comparable to Standard of Care Therapy
A small phase 2 study evaluated Debiopharm’s investigational antibiotic, afabicin, including its clinical response rate and safety profile of 2-3 weeks of treatment for staphylococcal bone and joint infections (BJI).
One source of bone and joint infections (BJI) can be from recent surgery including joint replacement procedures. It is estimated that over 2.9 million joint replacements are done globally every year.1
BJI include osteomyelitis, septic arthritis, and prosthetic joint infections and affect over 30,000 people per year within the US, UK, France, Germany, Spain and Italy combined.2
These infections can be especially troublesome to treat for a number of reasons including resistance to Staphylococcus aureus, blood flow sources to bones and also the time of treatment, which can typically be 4-6 weeks, with antibiotics that can cause toxicity and lead to adverse effects.
This last component of treatment toxicity can be very problematic according to Alireza Shamaei-Tousi, PhD, principal clinical scientist, Debiopharm.
"There is issues with safety and monitoring of some of these patients. For example, if you use vancomycin, it can be associated with cytopenia and ototoxicity,” Shamaei-Tousi said. "Also, if you use linezolid, because of cytopenia and other toxicity issues, the patient can only be given linezolid for 28 days. So you see there is an issue that becomes apparent if you want to have 6 weeks of treatment.”
Debiopharm, a privately-owned, Swiss-based, biopharmaceutical company is in a phase 2 trial evaluating its investigational antibiotic, afabicin, for the treatment of BJI due to staphylococci.
Shamaei-Tousi presented a poster, Results from A Phase 2 Clinical Trial for Treatment of Bone And Joint Infections with Afabicin, A First-in-Class Selective Anti-Staphylococcal Antibiotic, at the recent ID Week conference.
Study Results
This was a small study including 20 patients in the first cohort of the overall study and included 2-3 weeks of treatment.3
Shamaei-Tousi says afabacin is available in both IV and oral treatment. This might be an option for patients requiring longer treatment who may start with the former and can be switched to oral after discharge.
Study participants included in the study had osteomyelitis, septic arthritis, or prosthetic joint infections, and were randomized with 5 afabicin vs 1 standard of care (SoC) to receive IV and oral treatment for 14 to 21 days. Afabicin treatment was administered as 55 mg IV/ 80 mg PO BID, and was compared to a pre-defined SoC treatment, according to the investigators.3
Seventeen patients were administered afabicin and 3 were given SoC. The mean treatment duration was 20.1 days for the afabicin arm, and 19.7 days for the SoC arm. Osteomyelitis was identified in 85% of the participants, and Staphylococcus aureus was in 19 patients and 18 patients had methicillin-sensitive S aureus. 3
The investigators reported that all of the participants responded to treatment with a a clinical response at 4 weeks post end of treatment (EoT) was 13 of 15 patients in the afabicin arm. All 3 patients in the SOC arm achieved clinical response at 4 weeks post EoT. 3
At 12 weeks post EoT, the clinical response rate was 13 of 15 patients in the afabicin arm and 2 of 3 patients in the SoC arm. The investigators noted a similar safety profile was observed in the afabicin cohort vs the SoC cohort. 3
“The clinical response rate and safety profile of 2-3 weeks treatment of staphylococcal BJI with afabicin was comparable to SoC. These data support exploring longer durations of treatment in the study,” the investigators wrote.
The Company and the Compound
Debiopharm is working on treatments to cure cancer and treat infectious diseases. The company is developing microbiome-sparing pathogen-specific FabI inhibitors, a new class of antibiotics with novel mechanism of action. Afabicin, the most advanced FabI inhibitor in the pipeline, inhibits the fatty acid synthesis in staphylococci by targeting the Fabl enzyme. According to the Debiopharm, the therapy fulfills all 4 World Health Organization’s 2020 innovativeness criteria, including it’s a new chemical class, new target, a new mode of action and no cross-resistance to other antibiotic classes.
Next Steps
Afabicin is also being researched in staphylococcal acute bacterial skin and skin structure infections (ABSSSI). Debiopharm is continuing its studies of the investigational compound for BJI for patients requiring 4-6 weeks of treatment.
“The recruitment can be a bit of challenge, but we are hoping by next year, we have completed the cohort with 4-6 weeks of treatment,” said Shamaei-Tousi.
