A rigorous evaluation of the state of care for thyroid eye disease (TED) published in the American Journal of Ophthalmology (AJO) highlights the lack of current therapies to adequately treat the disease, according to an Horizon Therapeutics news release.
The invited ‘Perspective’ discusses the potential for Horizon’s investigational medicine teprotumumab to change the treatment paradigm. The Biologics License Application (BLA) for teprotumumab is currently being reviewed by the FDA and if approved, teprotumumab could be the first FDA-approved medicine for active TED. Teprotumumab is presently an investigational medicine and its safety and efficacy have not been established.
The review, “A New Era in the Treatment of Thyroid Eye Disease,” discusses the challenges in treating this serious, progressive and vision-threatening autoimmune disease with off-label therapies that address only inflammatory symptoms, and the considerable burden of illness TED places on patients. The authors highlight that the optimal time to initiate therapy is while the disease is active, which is a 1-to-3-year period characterized by inflammation. TED becomes inactive, and unresponsive to current pharmacotherapy, once the inflammation has stabilized. When TED is inactive, damage may be irreversible even with surgical interventions. This may result in permanent physical, visual, and psychosocial impairment.
Research implicates the overexpression of insulin-like growth factor-1 receptor (IGF-1R) as a key contributor to TED, suggesting the fully human monoclonal IGF-1R antagonist antibody teprotumumab inhibits a central mechanism driving the disease. Recent clinical studies with teprotumumab have demonstrated its potential in treating patients with active TED.
“There is no approved medical treatment for TED, and available options for TED, which focus only on managing inflammation and symptomatic relief, do not address the biology of the disease,” said Raymond Douglas, MD, PhD, director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center, senior author of the paper, and co-principal investigator of the phase 3 confirmatory clinical trial for teprotumumab. “Our foremost goal is to preserve patients’ vision, alleviate pain and avoid long-term, irreversible damage that could interfere with their daily function. The development of a targeted therapy such as teprotumumab serves as a potentially dramatic shift in the treatment paradigm.”
The body of clinical evidence with teprotumumab includes topline positive results from the phase 3 confirmatory clinical trial, called OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study), presented at the 2019 American Association of Clinical Endocrinologists (AACE) meeting, as well as positive phase 2 results. The OPTIC study found that significantly more patients treated with teprotumumab had a meaningful improvement in proptosis, or bulging of the eye, as compared with placebo (82.9% of teprotumumab patients compared to 9.5% of placebo patients). All secondary endpoints were also met, including reduced diplopia (double vision) and improved quality of life. Teprotumumab was generally well tolerated; the majority of adverse events were mild or moderate, manageable and resolved during or after treatment. The OPTIC study was initiated after clinically meaningful and highly statistically significant results from a Phase 2 study, published in The New England Journal of Medicine on May 4, 2017.
“Given advances in the understanding of the biological mechanisms of TED, our goal with teprotumumab is to offer an innovative and targeted solution for patients who currently suffer through the active phase of the disease and can be left with lifelong damage to their vision,” Shao-Lee Lin, MD, PhD, executive vice president, head of research and development and chief scientific officer, Horizon, said in the news release. “This review illustrates some of the critical attributes of teprotumumab that could fundamentally advance the state of care for this disease.”
Support for preparation of the manuscript was provided by Horizon.