Report results from the first cohort of TED patients treated with 2 intravenous infusions of 10 mg/kg VRDN-001 from our phase 1/2 double-masked randomized clinical trial (NCT05176639).  

IGF-1R antagonism can reduce TED-related inflammation and proptosis. We are evaluating VRDN-001, a full antagonist antibody to IGF-1R, in TED patients at doses of 3, 10, and 20 mg/kg.

Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 intravenous infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy were assessed. Endpoints included overall responder rate (% of subjects with ≥2 mm reduction in proptosis and ≥2 points reduction in CAS), proptosis responder rate (% of subjects with ≥2 mm improvement), change from baseline in proptosis and CAS, proportion of subjects with CAS decrease to 0 or 1, and diplopia resolution.

Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). After 2 infusions, the overall responder rate was 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). Proptosis responder rate was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). Proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo) and CAS decreased by 4.3 (VRDN-001) vs. 1.5 (placebo). CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). One case of transient hearing impairment that resolved by next visit, with normal audiometry, was reported. No serious AEs, hyperglycemia, or infusion reactions occurred.

Two infusions of 10 mg/kg VRDN-001 led to rapid, substantial improvement across all efficacy measures at 6 weeks in TED patients, surpassing 6-week results from prior RCTs of other anti-IGF-1R antibodies. Results from the additional 3 mg/kg and 20 mg/kg cohorts may extend these findings and define potential VRDN-001 treatment regimens.