100-OR: A Novel Macrophage-Regulation Drug for Treating Diabetic Foot Ulcer—A Phase III MRCT Study and Taiwan Experience

Abstract

Macrophage regulation plays an essential role in Diabetic foot ulcer (DFU) healing. By recognizing the therapeutic potential in M1/M2-macrophage-regulation for DFUs, we aim to investigate the efficacy and safety of ON101, a topical new drug with a M1/M2-macrophage-regulating mechanism in phase 3 MRCT across the US, China, and Taiwan (NCT01898923). There are 236 eligible subjects with Wagner Grade 1 or 2 DFU(s), randomized 1:1 to receive ON101 or comparator for up to 16 weeks, followed by a 12-week follow-up. The incidence of complete healing was 60.7% by ON101 and 35.1% by the comparator (P=0.0001). The time to complete ulcer healing was faster in the ON101 group (P=0.002). Since the high levels of HbA1C, ulcer persistence, ulcer location, and amputation history as the risk factors leading to poor DFU outcomes, ON101 also showed demonstrated robust efficacy and safety in hard-to-heal ulcers. ON101, approved by Taiwan FDA in 2021, was shown with excellent therapeutic efficacy and safety in the treatment of DFUs. In a real-world scenario, case collation from 133 patients, ulcer severity with Wagner grade 1 to 4, after applying ON101, the average ulcer complete healing rate is 71%, no adverse events were related to ON101, which validates the drug safety of ON101. ON101 further supports its excellent ability to promote wound healing in DFU patients with various severities (Wagner grade 1 to 4). All those patients who applied ON101 alone or with other therapies reached ulcer healing under infection control and with necessary debridement. Macrophage-regulating drug achieved superior therapeutic efficacy in a large Phase 3 MRCT and has demonstrated excellent therapeutic efficacy in the real-world scenario where Wagner grade 3 and 4 DFUs reached ulcer healing when ON101 was combined with other therapies. This enlightens the future treatment in Wagner grade 1 to 4 DFUs by macrophage immunomodulation new drug as a promising solution. Disclosure S.Chen: Employee; Oneness Biotech Co., Ltd. S.Chu: None. C.Pu: None. J.Chen: Employee; Oneness Biotech Company. Y.Wu: Employee; Oneness Biotech Co., Ltd.