SynOx Therapeutics has achieved a significant milestone in the development of emactuzumab for tenosynovial giant cell tumors (TGCT), completing patient enrollment in its pivotal Phase 3 TANGENT trial ahead of projected timelines. The Dublin, Oxford, and Philadelphia-based biopharmaceutical company announced that top-line data from the global, multi-center, randomized, double-blind, placebo-controlled registrational trial is expected in the first quarter of 2026.
Trial Design and Endpoints
The TANGENT study (ClinicalTrials.gov Identifier: NCT05417789) evaluates the efficacy and safety of emactuzumab in patients with TGCT who are not amenable to or would not benefit from surgery. Patients meeting eligibility criteria are randomized in a 2:1 fashion to receive either emactuzumab (1000 mg every two weeks for five doses) or matched placebo.
The primary endpoint is objective response rate (ORR) as assessed by RECIST criteria at six months post-randomization. Key secondary endpoints include patient-reported outcomes (PROMIS-PF), functional assessments of range of motion, pain, stiffness, durability of response, and safety. Patients are followed for two years from randomization, with those demonstrating disease progression after the six-month assessment eligible to receive open-label emactuzumab during follow-up.
Promising Clinical Profile
Emactuzumab is a humanized IgG1 monoclonal antibody targeting CSF-1R, designed to inhibit and deplete macrophages in tumor tissue. Originally developed by Roche, the compound has demonstrated substantial efficacy in clinical studies in TGCT, including an objective response rate of approximately 71%, rapid tumor reduction, functional improvement, and good tolerability with a manageable safety profile.
"Clinical evaluation to date has demonstrated the compound to be a promising, next-generation mAb therapy with the potential to offer a short treatment cycle, rapid onset and long duration of response that differentiates it from chronically administered oral agents," according to the company.
Addressing Significant Unmet Need
TGCT, previously termed pigmented villonodular synovitis (PVNS), is a rare, non-malignant but aggressively growing tumor of the synovium, tendon sheaths, and bursa membranes primarily located in knee, hip, and ankle joints. The condition is caused by excessive production of CSF-1 and represents a chronically debilitating disease that causes loss of function of the affected joints, as well as pain, stiffness, and limited range of motion.
While most patients undergo surgery, more than 50% of those with diffuse TGCT experience tumor recurrence within three years. If left untreated, TGCT can cause joint deformity, degenerative changes, and even lead to arthrodesis or amputation in severe cases.
Regulatory Recognition and Future Development
Earlier this year, SynOx received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA) for emactuzumab in the treatment of TGCT, recognizing the serious unmet medical need in this condition. Emactuzumab has also received Orphan Medicinal Product designation from the European Medicines Agency.
"Completion of enrollment in our registrational TANGENT trial marks an important milestone for SynOx and for the TGCT community," said Elyse Seltzer, M.D., Chief Medical Officer of SynOx Therapeutics. "We are deeply grateful to the patients, families, investigators, and clinical sites whose dedication has made this study possible and allowed SynOx to fully enroll the trial significantly ahead of our projected timeline."
Ray Barlow, Chief Executive Officer of SynOx, emphasized the transformational nature of this development: "This is a transformational time for SynOx as we advance emactuzumab through its pivotal Phase 3 program. We're excited about the next steps and look forward to delivering top-line data that we hope demonstrate how emactuzumab can transform care for patients with this grievous disease."
The company is actively exploring further development opportunities for emactuzumab in other macrophage-driven diseases, leveraging its mechanism of action as a CSF-1 receptor inhibitor. SynOx is backed by a strong syndicate of premier life science investors including Forbion, Gilde Healthcare, HealthCap, Bioqube Ventures and Medicxi.
