Recently presented Phase III clinical data show that teprotumumab significantly reduces double vision and improves the quality of life among patients with active thyroid eye disease (TED). Also known as Graves’ ophthalmopathy, the progressive autoimmune disease attacks the tissues behind the eyes (causing them to bulge outwards) and the muscles in the eyes, which become inflamed and scarred. Not only can the disease cause significant visual impairment, leading to a reduced ability to perform daily tasks, but the resulting changes in patients’ appearance can also affect mental health (1, 2).
Intriguingly, TED has only been shown to respond to pharmacotherapy in the “active” phase – characterized by inflammation and tissue expansion behind the eyes – which may last up to three years (3). The new data, presented at the American Society of Ophthalmic Plastic and Reconstructive Surgery’s (ASOPRS) 50th Anniversary Fall Scientific Symposium, show that teprotumumab, a fully human monoclonal antibody (mAb), can reduce several devastating effects of TED.
The disease itself is caused by autoantibodies activating a signaling complex that is mediated by insulin-like growth factor 1 receptors (IGF-1R) in the orbit of the eye (4, 5). Teprotumumab works by targeting – and blocking – those receptors, eliminating the manifestation of the disease.
The drug is currently being reviewed by the FDA, with the Prescription Drug User Fee Act (PDUFA) date set for March 8, 2020. If approved, teprotumumab would be the first FDA-approved medicine for the treatment of active TED. “Previously, patients might have been subjected to a variety of hydro-steroids and chronic treatments – and, later on, surgery. This would all be spread out over a five-year period. Now, this could potentially be condensed into one medical treatment with a series of infusions,” says Raymond Douglas of Cedars Sinai Medical Center, lead investigator of the OPTIC study.
The results of the Phase III trial, which took place at leading centers in the US, Germany and Italy, were promising: 68 percent of patients saw an improvement of at least one grade in double vision, with further improvements seen in other measures, such as quality of life, and a significant benefit of teprotumumab on proptosis (bulging eyes).
Douglas adds, “The aim of potentially reversing the disease process and reducing the need for surgery was a particularly lofty goal – one that had never been attempted before. The biggest surprise was that the drug actually worked so well and was so successful.”
References
- J Barrio-Barrio et al., “Graves’ Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management”, J Ophthal, 2015, 1 (2015). PMID: 26351570.
- L Bartalena et al., “The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy”, Euro Thyroid J, 5, 1 (2016). PMID: 27099835.
- WM Wiersinga, GJ Kahaly, “Graves’ Orbitopathy: A Multidisciplinary Approach – Questions and Answers”, Karger, 2017, 93 (2017).
- RS Bahn, “Graves’ Ophthalmopathy”, N Eng J Med, 2010. PMID: 20181974.
- J Pritchard et al., “Igs from patients with Graves’ disease induce the expression of T cell chemoattractants in their fibroblasts”, J Immunol, 168, 942 (2002). PMID: 11777993.
