Experimental drug holds promise for the treatment of thyroid eye disease



A phase 3 clinical trial shows promising results for an experimental drug called teprotumumab, which treats thyroid eye disease, researchers reported at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.

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“For the first time, there appears to be a medicine that can be given during the active phase of the disease and can actually reverse not just the eyelid swelling and the clinical activity score, but also reduce the eye bulging and double vision and [improve] the [patient’s] quality of life. It could be a watershed moment in the treatment of the disease,” said ophthalmologist Raymond Douglas, MD, PhD, professor of surgery at Cedar-Sinai Medical Center Los Angeles and the study’s coprincipal investigator, in an interview at the meeting.

According to Dr. Douglas, thyroid eye disease, which is also known as Graves’ eye disease, is a severely disabling condition that causes swelling, pain, discomfort, and blindness. “The burden really is quite significant,” he said, with an impact that’s been compared with that of breast cancer in quality-of-life studies.

“Current treatments for thyroid eye disease are rather limited,” he said. “They really encompass just reducing the swelling and the short-term manifestations of the disease. Treatments such as IV steroids and radiation have been shown to not have any effect on long-term manifestations such as eye bulging and double vision.”

Teprotumumab is a fully human monoclonal antibody that targets the insulinlike growth factor I receptor (IGF-IR). It seems to downregulate thyroid eye disease, Dr. Douglas said.

Researchers studied the drug in a randomized, placebo-controlled study: 41 patients were designated to receive eight intravenous infusions of the drug over 21 weeks (10 mg/kg for the first infusion, then 20 mg/kg thereafter). At week 24, 83% of the study group (34 of 41 patients) reached the endpoint of a reduction of eye bulging by at least 2 mm, compared with 10% of patients (4 of 42) in the placebo group, which received infusions of saline solution.

Two millimeters is significant, Dr. Douglas said. “If you noticed someone’s eye was bulging 2 millimeters, you’d say, ‘Hey, I think something is wrong with your eye.’ ”

Initial study results were released in February 2019. New data about secondary endpoints were released at the AACE meeting: Researchers reported that the average reduction in proptosis (eye bulging) was 2.82 mm in the study group, compared with 0.54 mm in the placebo group (P less than .001).

Dr. Douglas said he can “achieve 3 mm of reduction through surgery to drill out the bone between the eye and the brain. [The patients in the study group] were able to achieve almost 3 millimeters of reduction by the drug alone. It’s a rather significant improvement.”

The new data also provided some insight into the timing of clinical improvements. According to Dr. Douglas, “most of the endpoints were met as early as 6 weeks or [after] two infusions of this drug.”

The adverse effects were relatively mild and included muscle spasms, said Dr. Douglas. The side effects seem to be “well tolerated,” he noted, and none led to cessation of therapy.

Participants with potential for motherhood or fatherhood during the trial had to agree to take precautions to avoid becoming pregnant or impregnating a partner.

Dr. Douglas didn’t provide cost information about the drug. However, it seems likely to be expensive. A writer with Seeking Alpha, a stock market analysis site, estimated that the cost could reach “$250,000 or $300,000 per patient per year, which translates to a $3.7 billion to $6 billion market in the United States alone (based on the estimated patient population in the 15,000-20,000 range).”

The drug’s manufacturer, Horizon Therapeutics, expects to apply to the Food and Drug Administration later this year for approval of the drug.

If it is approved, endocrinologists will have an opportunity to partner with eye surgeons to treat thyroid eye disease, Dr. Douglas said. “The crux will be the comanagement with the endocrinologist helping to control the thyroid function and manage some of the side effects of this medication, and the oculoplastic surgeon [working on] diagnosis, appropriate use, and management.”

Horizon Therapeutics funded the study. Dr. Douglas disclosed that he is a consultant with the company.

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