Acelyrin, Inc. announced positive proof-of-concept data from its Phase 1/2 clinical trial of lonigutamab in patients with thyroid eye disease (TED). The data, shared as a late-breaking oral presentation at the Endocrine Society’s Annual Meeting (ENDO 2024), highlight the potential of lonigutamab as a novel treatment for this vision-threatening autoimmune condition.
Lonigutamab is a humanized IgG1 monoclonal antibody administered subcutaneously, targeting the insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R is an FDA-approved mechanism for treating TED. The Phase 1/2 trial (NCT05683496) is a multi-center study evaluating the safety and efficacy of lonigutamab in three cohorts of patients with active TED. Cohort 1 is placebo-controlled, testing 40mg every three weeks (Q3W) through six weeks. Cohort 2 is open label, testing a 50mg loading dose followed by 25mg every week (QW), and cohort 3 is open label, testing every four weeks (Q4W) dosing.
Dosing and Mechanism of Action
Lonigutamab differentiates itself through its subcutaneous delivery and unique binding epitope on IGF-1R. Preclinical data suggest it is 75-fold more potent than the current standard of care in binding and functional laboratory assays, leading to rapid receptor internalization. This subcutaneous administration potentially allows for longer-term dosing, which could improve the depth and durability of clinical responses.
Thyroid Eye Disease (TED) Context
TED is a progressive, chronic inflammatory disease affecting over 100,000 people in the United States. It involves inflammation and tissue expansion behind the eye, leading to proptosis (eye bulging) and potential inability to close the eyelids. Diplopia (double vision) and compression of the retinal nerve, potentially causing blindness, are also significant risks. Current treatments aim to manage inflammation and prevent vision loss, but there remains a need for therapies that offer deeper and more durable responses.
Presentation Details
The presentation, titled "Preliminary Safety And Efficacy Of Subcutaneous Lonigutamab (anti-IGF-1R) From A Phase 1/2 Proof Of Concept Study In Patients With Thyroid Eye Disease," was delivered by Dr. Shoaib Ugradar from the Jules Stein Eye Institute, University of California, on June 3rd. The data shared provided an early glimpse into the potential of lonigutamab to address the unmet needs in TED treatment.
