The US Food and Drug Administration (FDA) has approved the monoclonal antibody teprotumumab (Tepezza, Horizon Therapeutics) for the treatment of adults with thyroid eye disease.

Thyroid eye disease is a serious, progressive, vision-threatening autoimmune condition that can cause proptosis (bulging), strabismus (eye misalignment), eye pain, light sensitivity, double vision, and in some cases blindness. The only possible treatments until now have been steroids and surgery.

Believed to occur in about 15,000 to 20,000 Americans annually, thyroid eye disease is most often associated with hyperthyroidism or Graves' disease. However, it arises from a separate process involving autoantibodies that activate an insulinlike growth factor 1 receptor–mediated signaling complex on cells within the eye orbit.

Teprotumumab, given in eight infusions once every 3 weeks, blocks that receptor.

The FDA approval is based on results from two clinical trials previously reported by Medscape Medical News. Findings from a phase 2 study that involved 42 patients with moderate to severe thyroid-associated ophthalmopathy showed significant improvements with treatment with teprotumumab that lasted up to 72 weeks.

In the subsequent confirmatory phase 3 multinational OPTIC trial, as reported by Medscape Medical News, at 24 weeks, significantly more of the 41 patients treated with teprotumumab experienced 2-mm or greater reduction in proptosis without deterioration in the other eye (82.9% vs 9.5% of the 42 patients given placebo; P < .001).

Significant improvements were also seen in other measured outcomes, including orbital pain, eyelid swelling, diplopia, and quality-of-life scores.

The OPTIC trial has just been published in the New England Journal of Medicine.

"Today's approval marks an important milestone for the treatment of thyroid eye disease. Currently, there are very limited treatment options for this potentially debilitating disease. This treatment has the potential to alter the course of the disease, potentially sparing patients from needing multiple invasive surgeries by providing an alternative, non-surgical treatment option," said Wiley Chambers, MD, deputy director of the Division of Transplant and Ophthalmology Products in the FDA's Center for Drug Evaluation and Research, in a press release issued by the agency.

In a Horizon Pharma statement, Jeff Todd, president and chief executive officer, Prevent Blindness, said teprotumumab "is a much-needed breakthrough for a community of people who have historically had to struggle in pain as their symptoms progress ― risking permanent damage to their eyes and making it extremely difficult to go about their daily lives.

"This approval is meaningful to our organization because we are committed to helping patients with vision impairment and those who are at significant risk," he added.

Graves' Opthalmology: A Rare Disease

In December 2019, the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee unanimously voted in favor of approving teprotumumab. It had been granted fast-track status in April 2015 and breakthrough therapy designation in July 2016. It received orphan drug designation on June 19, 2019.

The approval comes ahead of the Prescription Drug User Fee Act (PDUFA) goal date of March 8, 2020.

"Thyroid eye disease is a rare disease that impacts a small percentage of the population," Chambers noted, "and for a variety of reasons, treatments for rare diseases are often unavailable. This approval represents important progress in the approval of effective treatments for rare diseases, such as thyroid eye disease."

Adverse events of teprotumumab include muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing loss, dry skin, dysgeusia (altered sense of taste), and headache. The majority of these events were graded mild to moderate and were manageable in the trials, with few discontinuations or therapy interruptions.

The drug is contraindicated during pregnancy.

Per the advisory panel's discussion, Horizon will conduct a postmarketing study to evaluate safety in a larger patient population and will evaluate retreatment rates relative to treatment duration.

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