Pooled Data Confirm Benefit of Teprotumumab for Thyroid Eye Disease

By Reuters Staff

April 23, 2021

NEW YORK (Reuters Health) - Pooled clinical-trial data show that teprotumumab improves eye bulging and double vision in patients with active thyroid eye disease, with most patients having long-lasting responses.

The data clearly show that teprotumumab "mitigates varying levels of disease severity, including proptosis and diplopia, which are the most progressive and difficult findings to treat, and that improvements continue for the long term," Dr. George Kahaly of the Johannes Gutenberg University Medical Center in Mainz, Germany, said in a news release from Horizon Therapeutics, which makes the drug and funded the studies and the new analysis.

Thyroid eye disease (TED) - also known as thyroid-associated ophthalmopathy, Graves' ophthalmopathy, and Graves' orbitopathy - is a rare vision-threatening autoimmune disease.

Teprotumumab is a fully human monoclonal antibody that inhibits insulin-like growth factor-1 receptor (IGF-1R). In 2020, it became the first drug approved by the U.S. Food and Drug Administration (FDA) for TED.

In The Lancet Diabetes and Endocrinology, Dr. Kahaly and colleagues report efficacy and safety data from two 24-week multicenter, double-blind, placebo-controlled clinical trials in 171 patients with active, moderate-to-severe TED; 84 received teprotumumab and 87 received placebo once every three weeks for a total of eight infusions.

According to the authors, "all objective signs and symptoms of thyroid eye disease, especially proptosis and diplopia, which can be resistant to medical therapy, were markedly and significantly improved with teprotumumab."

"The findings were maintained for nearly 1 year following drug discontinuation in most patients. High-risk patient subgroup analyses confirmed that efficacy was independent of sex, age, tobacco use, and disease duration or severity. Furthermore, these responses were associated with substantial moderate-to-large improvements in the overall Graves' ophthalmopathy quality of life (GO-QOL) score," Dr. Kahaly and colleagues report.

Teproptumumab was well tolerated, with mild-to-moderate (grade 1 or 2) adverse events during the treatment period. The most common adverse events with the greatest risk difference from placebo were muscle spasm (18%), hearing loss (10%) and hyperglycemia (8%). Three possibly related serious adverse events (diarrhea, infusion reaction, and Hashimoto's encephalopathy (co-occurring with confusion) led to study discontinuation.

The authors of a linked editorial say the current evidence "clearly indicates that teprotumumab positively and durably improves the course of active, moderate-to-severe, thyroid eye disease."

"Although these are exciting results, the role of teprotumumab in the armamentarium of treatment options for thyroid eye disease requires further clarification," write Dr. Tomasz Bednarczuk of the Medical University of Warsaw in Poland and Dr. Simon Pearce of Newcastle University, in Newcastle upon Tyne in the U.K.

They note that high-dose intravenous pulsed glucocorticoid therapy has been the standard first-line treatment for active thyroid eye disease for more than a decade and is inexpensive (roughly US$30 for one 500 mg powder for injection, and $360 for a 12-week course of treatment).

In contrast, teprotumumab costs about $15,000 for one 500 mg powder for injection and about $300,000 for the course of treatment depending on patient's weight.

"At the current price, teprotumumab seems unlikely to be widely used as a first-line therapy for thyroid eye disease in many countries, unless head-to-head trials can show its superiority to high-dose intravenous glucocorticoids with respect to greater efficacy (including a reduction in subsequent second-line treatments and surgical procedures), better safety, and greater cost-effectiveness," Drs. Bednarczuk and Pearce write.

"Comparisons with future disease-modifying drugs for thyroid eye disease, including thyroid-stimulating hormone receptor-specific treatment modalities (eg, monoclonal antibodies and small molecules) in the development pipeline will also be important. Hopefully, teprotumumab and future disease-modifying drugs alongside established immunosuppressive treatments will lead to personalized medicine in thyroid eye disease," they conclude.

Several of the authors have financial relationships with Horizon Therapeutics.

SOURCE: https://bit.ly/3neX0Ac https://bit.ly/3xcjeqR Lancet Diabetes and Endocrinology, online April 15, 2021.