Phaxiam Therapeutics has announced clinical data from its PhagoDAIR pilot study, revealing encouraging results for phage therapy in treating Staphylococcus aureus prosthetic joint infections (PJI). The study, while facing randomization challenges, demonstrated a 74% infection control rate in the phage treatment arm, highlighting the potential of this innovative approach.
The PhagoDAIR I study was a pilot, randomized, multicenter, non-comparative, double-blind study involving patients with hip or knee prosthesis infections caused by Staphylococcus aureus occurring more than one month after prosthesis insertion. All patients underwent debridement, antibiotic therapy, and prosthesis retention (DAIR), the standard of care. Participants were then randomized to receive either anti-S. aureus phages via intra-articular injection or a placebo, in addition to the standard DAIR procedure.
The primary endpoint was the percentage of patients in each treatment arm free of infectious relapse at 12 weeks. Of the 26 evaluable patients, 14 out of 19 (74%) in the phage arm achieved a positive infection control rate, compared to 5 out of 7 (71%) in the placebo arm, where antibiotics were administered alone. The study's design included 20 patients in the "Phages" arm and only 9 in the placebo arm, which the company attributed to stratification by center and prosthesis location, combined with small numbers and many clinical centers having recruited only one or two patients, explain this imbalance, making it difficult to analyze the study's primary objective in the placebo arm.
Safety and Tolerance
Tolerance analysis of the 29 randomized patients confirmed the safety of phages, consistent with observations from Data Safety Monitoring Board (DSMB) meetings, which supported the study's continuation.
Rescue Medication
Among the seven patients who experienced relapse, four (three in the phage arm and one in the placebo arm) received rescue medication consisting of weekly phage administrations for three weeks. Two of these four patients did not relapse within three months of the rescue treatment.
The consolidated infection control rate, considering patients who received phages during DAIR or as a rescue medication, reached 80% (16/20). These findings support the decision to maintain the same treatment regimen in the upcoming GLORIA Phase II study.
GLORIA Phase II Study
Building on the PhagoDAIR study, Phaxiam is advancing its phage therapy program with the GLORIA Phase II study, a global, multicenter, randomized, placebo-controlled trial. The study aims to enroll 100 patients with PJI undergoing open surgical debridement (DAIR), irrespective of the time between prosthesis placement and S. aureus infection onset. Patients will receive three intra-articular injections of Phaxiam's anti-S. aureus phages or a placebo, combined with a 12-week antibiotic therapy, without suppressive antibiotic therapy.
Pascal Birman, PHAXIAM's Chief Medical Officer, expressed confidence in the GLORIA study, stating that it would address the inclusion challenges and randomization complexities encountered in the PhagoDAIR study by targeting a larger patient population and employing a more appropriate statistical methodology. The GLORIA study is scheduled to commence in Q1 2025 across seven European countries and the United States, pending regulatory approvals, including IND approval from the US FDA and review by European health authorities.
Pr. Tristan Ferry, Coordinator of the Referral Center for the Management of Complex Bone and Joint Infection (CRIOAC) at Hôpital de la Croix-Rousse (HCL, Lyon), highlighted the consistency of the phage arm's clinical activity (~75%) with real-world data from compassionate treatments. He also noted the positive outcomes in relapsed patients who received rescue medication.
