20-LB: A M1/M2-Macrophages Regulating New Drug in an International Phase 3 Study

The healing of diabetic foot ulcers (DFUs) stalled in inflammation stage due to overabundance of inflammatory macrophages and the dysregulated M1/M2 macrophages in the lesion. Restoring the balance of M1/M2 macrophages plays a critical role in orchestrating the healing process of DFUs. By recognizing the therapeutic potential in M1/M2-macrophage-regulation for DFUs, we aim to evaluate the efficacy and safety of ON101, a topical new drug with M1/M2-macrophage-regulating mechanism versus a hydrocolloid dressing in an international, multicenter, randomized, controlled, evaluator-blind phase 3 study in 21 clinical/medical centers across the US, China, and Taiwan by following Guidance for Industry Chronic Cutaneous Ulcer and Burn Wounds — Developing Products for Treatment. 236 eligible patients with post-debrided DFU(s) between 1 - 25 cm², present for ≥4 weeks and Wagner Grade 1 or 2, were randomized 1:1 to receive ON101 or comparator for up to 16 weeks followed by a 12-week follow-up. Baseline demography and medical history between the two groups were well balanced. The incidence of complete healing as the primary endpoint in full analysis set was 60.7% by ON101 and 35.1% by the comparator during the treatment period (p=0.0001). Time to complete ulcer healing as the secondary endpoint was noted faster in the ON101 group (p=0.002). No significant changes or differences between the two treatment groups in hematology, biochemistry (including HbA_1c and fasting glucose), or vital signs. Related treatment of emergent adverse events was reported in 7 patients (5.7%) in the ON101 group and 5 (4.4%) from the comparator group. None of the serious adverse events was related to ON101 while there was a case of osteomyelitis reported to be related to the comparator. ON101, recently approved by Taiwan Food and Drug Administration, was shown with clinically significant efficacy and well-tolerated safety profile in DFUs which provides not only a new prospect in DFU management but a differentiated approach towards active-healing.