June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Phase 1/2 Study of Treatment Response With VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor, in Patients with Thyroid Eye Disease (TED)
Author Affiliations & Notes
  • Roger Eric Turbin
    Rutgers New Jersey Medical School, Dept of Ophthalmology, New Jersey, United States
  • Raymond Douglas
    Cedars Sinai Medical Center, California, United States
  • Shoaib Ugradar
    The UCLA Stein Eye Institute, California, United States
  • Kimberly Cockerham
    Stanford Department of Ophthalmology at Byers Eye Institute, California, United States
  • Jade Schiffman
    Neuroeye Diagnostic PA, Texas, United States
  • Navdeep Nijhawan
    Oshawa Clinic, Ontario, Canada
  • Denis J. O'Shaughnessy
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Rochelle M. Summerfelt
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Angela She
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Barrett Katz
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Roger Turbin Viridian Therapeutics, Horizon Therapeutics, Medtronic, Code F (Financial Support), Moderna, Biogen, Roche, Merck, Titan, Pfizer, Viridian Therapeutics, Code I (Personal Financial Interest), Viridian Therapeutics, Code R (Recipient); Raymond Douglas Viridian Therapeutics, Horizon Therapeutics, Code C (Consultant/Contractor), Viridian Therapeutics, Horizon Therapeutics, Code F (Financial Support); Shoaib Ugradar Viridian Therapeutics, Valenza Bio, Code C (Consultant/Contractor); Kimberly Cockerham Viridian Therapeutics, Horizon Therapeutics, Immunovant, Code C (Consultant/Contractor), Viridian Therapeutics, Code F (Financial Support); Jade Schiffman Viridian Therapeutics Inc., Code F (Financial Support); Navdeep Nijhawan Viridian Therapeutics, Code C (Consultant/Contractor); Denis J. O'Shaughnessy Viridian Therapeutics, Code E (Employment); Rochelle M. Summerfelt Viridian Therapeutics, Code E (Employment); Angela She Viridian Therapeutics, Code E (Employment), Viridian Therapeutics, Code P (Patent); Barrett Katz Viridian Therapeutics, Code E (Employment)
  • Footnotes
    Support  This study was sponsored by Viridian Therapeutics Inc.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5432. doi:
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      Roger Eric Turbin, Raymond Douglas, Shoaib Ugradar, Kimberly Cockerham, Jade Schiffman, Navdeep Nijhawan, Denis J. O'Shaughnessy, Rochelle M. Summerfelt, Angela She, Barrett Katz; Phase 1/2 Study of Treatment Response With VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor, in Patients with Thyroid Eye Disease (TED). Invest. Ophthalmol. Vis. Sci. 2023;64(8):5432.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : IGF-1 receptor (IGF-1R) antagonism reduces TED-related inflammation and proptosis. VRDN-001, a high-affinity antagonist antibody to IGF-1R that fully inhibits IGF-1R signaling, is being evaluated in a phase 1/2 RCT (NCT05176639) at 3-20 mg/kg. We present results from the first cohort of TED patients (10 mg/kg).

Methods : Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (PBO; 3:1). Safety, tolerability, and efficacy through 12 weeks were assessed.

Results : Baseline characteristics were similar between VRDN-001 (n=6) and PBO (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% (0/2; PBO); proptosis responder rate (% of patients with ≥2 mm reduction) was 83% (5/6; VRDN-001) vs. 50% (1/2; PBO). 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 (PBO) 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 for whom scans were available and showed no improvement in both PBO patients. CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; PBO) at 6 weeks; 80% (4/5) of VRDN-001 maintained CAS of 0 or 1 at 12 weeks. Mean reduction in CAS was 4.3 (VRDN-001) vs. 1.5 (PBO) at 6 weeks and remained consistent for VRDN-001 at 12 weeks (4.2). In the 4 VRDN-001 patients presenting with diplopia, complete resolution occurred for 3 by 6 weeks and all by 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.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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