Minghui Pharmaceutical's MHB018A, a novel subcutaneous VHH-Fc fusion protein targeting the insulin-like growth factor-1 receptor (IGF-1R), has shown positive topline results in a Phase Ib/II clinical trial for patients with active, moderate-to-severe Thyroid Eye Disease (TED). The multicenter, double-blind, randomized, placebo-controlled trial evaluated the safety and preliminary efficacy of MHB018A across three different dosing regimens.
The study enrolled 30 participants who were sequentially assigned to three dose groups: 300 mg fixed-dose every four weeks (Q4W) for three doses, 450 mg fixed-dose Q4W for three doses, and a 600 mg loading dose followed by two 300 mg fixed-dose Q4W. Within each group, participants were randomized in a 4:1 ratio to receive subcutaneous injections of either MHB018A or placebo.
Proptosis Reduction and Clinical Activity
The primary endpoint, proptosis response rate (≥2 mm reduction from baseline at week 12), was 50.0%, 50.0%, and 87.5% for the 300 mg, 600 mg + 300 mg, and 450 mg groups, respectively, compared to 16.7% in the placebo group. Notably, the 450 mg group exhibited rapid responses, with 50.0% and 87.5% of patients achieving a ≥2 mm reduction in proptosis at weeks 4 and 8, respectively.
Clinical benefit was further supported by improvements in overall response rate (≥2 mm proptosis reduction and ≥2-point improvement in clinical activity score (CAS)) and the percentage of subjects achieving a CAS of 0 or 1. MHB018A demonstrated significant improvements across all these parameters compared to placebo.
Safety and Tolerability
MHB018A was generally well-tolerated across all dose regimens. Most adverse events (AEs) were Grade 1 or 2 in severity and resolved without intervention after treatment completion. No severe hearing impairment was reported, and the overall safety profile was consistent with that of other IGF-1R antibodies.
Future Directions
"We are highly encouraged by these results, which demonstrate that subcutaneous administration of MHB018A delivers faster, deeper, and more robust responses in TED patients, particularly at the 450 mg dose," said Guoqing Cao, Ph.D., Chief Executive Officer at Minghui Pharmaceutical. "Building on these encouraging results, we plan to initiate Phase 3 registrational trials in the first half of 2025."
These Phase Ib/II results suggest that MHB018A could represent a significant advancement in TED care, offering a potentially more effective and well-tolerated subcutaneous treatment option. Thyroid eye disease, an autoimmune disorder driven by autoantibodies targeting thyroid receptors, affects a significant population, and the IGF-1R has been validated as an effective therapeutic target.
