ECE2023 Poster Presentations Thyroid (163 abstracts)
Treatment Response With VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor, in Thyroid Eye Disease (TED): Phase 1/2 Clinical Study
Barrett Katz 1 , Roger Turbin 2 , Kimberly Cockerham 3 , Rosa Tang 4 , Navdeep Nijhawan 5 , Shoaib Ugradar 6 , Denis J. O’Shaughnessy 1 , Rochelle M. Summerfelt 1 , Angela She 1 & Raymond Douglas 7
1Viridian Therapeutics, Inc., Waltham, United States; 2Rutgers New Jersey Medical School, Department of Ophthalmology, New Jersey, United States; 3Stanford Department of Ophthalmology at Byers Eye Institute, Stanford, United States; 4Eye Wellness Center– Neuro-Eye Clinical Trials, Inc., Bellaire, United States; 5Oshawa Clinic, Oshawa, United States; 6The UCLA Stein Eye Institute, Los Angeles, United States; 7Cedars Sinai Medical Center, Los Angeles, United States
Purpose: IGF-1R antagonism reduces TED-related inflammation and proptosis. VRDN-001, a subnanomolar affinity full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 RCT (NCT05176639) at 3-20 mg/kg. We present results from the first cohort (10 mg/kg) of TED patients.
Methods: Adults with active moderate-to-severe TED with clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy through 12 weeks were assessed.
Results: Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). At 6 weeks, overall responder rate (% of patients with ≥2 mm reduction in proptosis and ≥2 point reduction in CAS) was 83% (5/6; VRDN-001) vs. 0% (placebo); proptosis responder rate (% of patients with ≥2 mm reduction) was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). At 12 weeks, 80% (4/5) of VRDN-001 responders had maintained both overall and proptosis response. Mean proptosis reduction was 2.4 mm (VRDN-001) vs. 1.0 mm (placebo) at 6 weeks and remained consistent for VRDN-001 at 12 weeks (2.2 mm). MRI analysis at both 6 and 12 weeks confirmed proptosis improvement for all 4 VRDN-001 patients with scans available and showed no improvement in both placebo patients. CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (placebo) at 6 weeks and was maintained for 80% (4/5) at 12 weeks. Mean reduction in CAS was 4.3 (VRDN-001) vs. 1.5 (placebo) at 6 weeks and remained consistent for VRDN-001 at 12 weeks (4.2). Of the 4 VRDN-001 patients presenting with diplopia, complete resolution occurred for 3 by 6 weeks and all by 12 weeks. VRDN-001 was well-tolerated through 12 weeks. AEs were mostly mild, with no severe or serious AEs reported.
Conclusions: Two infusions of 10 mg/kg VRDN-001 were well tolerated in this cohort of TED patients, and the rapid, clinically meaningful improvement across all efficacy measures by 6 weeks was sustained through 12 weeks. These results were achieved with a lower dose and fewer treatments than in 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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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