Elegrobart reduces proptosis in active thyroid eye disease

Efficacy and Safety of Subcutaneous Elegrobart in Active Thyroid Eye Disease: Topline Results from the Phase 3 REVEAL-1 Trial

Background and Clinical Context

Thyroid eye disease (TED), frequently associated with Graves’ disease, is a progressive, debilitating autoimmune condition characterized by the activation of orbital fibroblasts. This activation leads to inflammation, expansion of extraocular muscles, and accumulation of hyaluronan within the orbital space. Clinically, this manifests as proptosis (ocular bulging), severe diplopia (double vision), periorbital edema, and in severe cases, compressive optic neuropathy.

Historically, the management of moderate-to-severe TED relied heavily on systemic corticosteroids and orbital radiotherapy, both of which possess significant adverse effect profiles and limited disease-modifying efficacy. The advent of targeted biologic therapies, specifically insulin-like growth factor 1 receptor (IGF-1R) inhibitors, has revolutionized TED management. However, existing therapies often require frequent, prolonged intravenous (IV) infusions, presenting a significant logistical burden for patients and healthcare systems.

Elegrobart (Viridian Therapeutics) represents a novel therapeutic approach. It is a half-life extended monoclonal antibody engineered to antagonize the IGF-1R, formulated specifically for subcutaneous administration. The phase 3 REVEAL-1 trial evaluated the efficacy and safety of this agent in patients with active TED, aiming to establish a more accessible, lower-burden treatment paradigm.

Study Design and Patient Population

The REVEAL-1 trial was a randomized, double-blind, placebo-controlled phase 3 investigation enrolling 132 adult patients diagnosed with active thyroid eye disease. Participants were randomized into one of three distinct study arms for a 24-week observation period:

1. Elegrobart Q4W: Subcutaneous administration every 4 weeks.

2. Elegrobart Q8W: Subcutaneous administration every 8 weeks.

3. Placebo: Matched subcutaneous placebo injections.

The primary efficacy endpoint was the proptosis response rate at 24 weeks, conventionally defined as a reduction of at least 2 millimeters (mm) in proptosis from baseline in the study eye, without a corresponding $\ge$2 mm increase in the fellow eye.

Efficacy Outcomes: Proptosis and Diplopia

Topline results demonstrated robust, statistically significant reductions in proptosis and visual impairment across both active treatment arms compared to placebo.

Table 1. Proptosis Response and Mean Reduction at 24 Weeks

Note: Proptosis measurements were rigorously confirmed utilizing both standardized exophthalmometry and orbital magnetic resonance imaging (MRI).

Improvements in extraocular muscle function and subsequent reduction in diplopia were similarly pronounced, particularly in the highly frequent dosing cohort.

Table 2. Diplopia Outcomes at 24 Weeks

Safety Profile and Tolerability

The safety profile of elegrobart was consistent with the established class effects of IGF-1R antagonism. The drug was generally well tolerated across both subcutaneous dosing regimens. A notable adverse event of interest for this pharmacological class is hearing impairment.

Table 3. Placebo-Adjusted Hearing Impairment Rates