The Quest for a Graves’ Disease Treatment: Kellogg Eye Center Contributes to Study of Teprotumumab

Syringe with drugs for Graves’ disease treatment

Graves’ eye disease is known as thyroid eye disease. The University of Michigan Kellogg Eye Center is working on an investigational therapy that might not only improve inflammation conditions but also lessen the severity and offer a new patient outcome.

The University of Michigan, Kellogg Eye Center scientific director Terry J. Smith, MD is one the nation’s leading Graves’ disease specialists—he is the only endocrinologist with a full-time faculty appointment at an academic eye center reports the Michigan Health Lab blog. 

Graves’ Disease

Also known as toxic diffuse goiter, it is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea, and unintentional weight loss. Other symptoms may include thickening of the skin n the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves’ ophthalmopathy. About 25 to 80% of people with the condition develop eye problems. 

Graves’ disease occurs in about 0.5% of peopleIt occurs 7.5 times more often in women than in men. It often starts between 40 and 60 years of age. It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).

Dr. Terry J. Smith

While at the University of California, Los Angeles he made basic science discoveries involving teprotumumab, a human monoclonal antibody. Originally developed as a cancer drug, it failed to exhibit efficacy in patients with cancer, but some researchers suspected it could help interrupt Graves’ eye disease process. Smith embraced the potential. Smith is an investigator participating in the OPTIC trial.


A complex protein that works by inhibiting the insulin-like growth factor I receptor (IGF-1R); and a signaling pathway in the orbital cells of patients with Graves’ eye disease. It is being developed by Horizon Therapeutics and known as HZN-001

The Study

In a recent study, 83 patients were enrolled in the Phase 3 OPTIC trial and received eight intravenous infusions of teprotumumab or placebo every three weeks for up to 21 weeks.

83% of the teprotumumab-treated patients in the OPTIC trial demonstrated at least a 2-millimeter reduction of proptosis in their more severely affected eye. Observers are hopeful that patients with Graves’ eye disease may soon have a new treatment option.

The Sponsor

Horizon Therapeutics is the drug company sponsor. They plan on submitting a biologics license application to the FDA later in 2019. Their drug has been given breakthrough status which could fast-track its review.

At just over $1 billion in revenue, the sponsor is an Irish-tax registered biopharma company that acquired, rebrands, repackages and reprices specialist drugs for sale into the U.S. healthcare system, which represents the great majority of its worldwide sales. 

Its drug portfolio is focused on treatments for arthritis, pain and inflammatory diseases. Its portfolio includes Actimmune (interferon gamma), Duexis (ibuprofen+ famotidine), Pennsaid (diclofenac, 2% topical) and Rayos/Lodotra (prednisone). The company is a member of Pharmaceutical Research Manufacturers of America (PhRMA). 

Lead Investigators

Although the University of Michigan participated, the lead investigators for the study included Cedars-Sinai Medical Center, in Los Angeles and Johannes Gutenberg Medical Center in Mainz, Germany. Co-principal investigator Raymond Douglas, MD, Ph.D., and director of the orbital and thyroid eye disease programs at Cedars-Sinai Medical Center noted: “In the study, patients treated with teprotumumab had an unprecedented reduction in the proptosis, which is currently only treatable via surgery after the active disease has ended.”

Dr. Douglas continued “If approved, teprotumumab would give physicians the first medicine show to reduce eye bulging during active thyroid eye disease, in addition to treating other painful symptoms.”

Raymond Douglas, MD, Ph.D. 

George Kahaly, MD, Ph.D.