MRI/CT Analysis Shows Potential for Disease-Modifying Effects of VRDN-001, a Targeted TED Therapy: Reduced Proptosis and Muscle/Fat Volume in a Proof-of-Concept Study in TED
Author: Shoaib Ugradar
Base Hospital / Institution: Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA
Rapid fire oral presentation
Abstract ID: 24-296
Purpose
VRDN-001 is a full antagonist monoclonal antibody targeting the IGF-1 receptor in development for thyroid eye disease (TED). Clinical outcomes from a small phase 2 proof-of-concept study of VRDN-001 in active TED have been previously presented. This MRI/CT analysis explores the potential disease-modifying effects on key components of TED pathophysiology (enlarged orbital muscle and fat) in patients from the phase 2 study.
Methods
Patients with active TED treated with 2 IV infusions of 10 mg/kg VRDN-001 or placebo at Weeks 0 and 3 in a phase 2 proof-of-concept study were included. Preliminary MRI/CT mean changes from baseline in proptosis, extraocular muscle volume (EOM), and orbital fat volume (OF) were assessed at Weeks 6 and 12 for all eyes.
Results
VRDN-001 was generally well tolerated with no severe or serious adverse events. A total of 4/6 VRDN-001-treated patients (8 eyes) and 5/5 placebo patients (10 eyes at Week 6, 8 eyes at Week 12) had evaluable MRI/CT scans; the 2 unevaluable scans had poor image quality. Mean changes from baseline at 6 weeks for VRDN-001 vs placebo were -4.6 mm vs -0.2 mm (proptosis), -31% vs -10% (EOM), and -19% vs -2% (OF); changes at 12 weeks were -5.9 mm vs -0.1 mm (proptosis), -37% vs -17% (EOM), and -37% vs 0% (OF).
Conclusion
In this small number of patients with active TED, MRI/CT analysis shows potential for a disease-modifying effect of VRDN-001, with reductions of EOM and OF associated with improvements in proptosis at 6 weeks that continued through 12 weeks (9 weeks beyond last treatment).
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| Andrea | Kossler | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Roger | Turbin | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Kimberly | Cockerham | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Navdeep | Nijhawan | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Rosa | Tang | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Michael | Yen | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Chantal | Boisvert | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| David | Kaufman | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Wendy | Lee | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Michael | Yoon | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Cathy | Michalsky | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
| Thomas | Ciulla | Department of Orbital and Oculoplastic Surgery, Private Practice, Beverly Hills, CA |
