FDA Panel to Review First Thyroid Eye Disease Drug

Whether teprotumumab's benefits in thyroid eye disease outweigh risks for muscle spasm and worsened bowel inflammation will be voted upon at Friday's meeting of the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee.

Surgery is now the only treatment for active thyroid eye disease, so teprotumumab infusions would be the first drug treatment option for the potentially blinding condition.

"There is a significant unmet need for a pharmacologic treatment that reduces proptosis, diplopia and inflammation and has a favorable benefit-risk profile in this debilitating, vision-threatening and disfiguring disease," according to briefing documents submitted by the applicant.

Developed by Horizon Pharma, the fully human monoclonal antibody acts as an insulin-like growth factor-1 receptor inhibitor, reducing the autoimmune and inflammatory response leading to the proptosis -- i.e., bulging of the eyes -- associated with Graves' orbitopathy.

Delivered in eight intravenous infusions, teprotumumab was effective in two trials for reducing proptosis in patients with active thyroid eye disease.

In the first study of 88 patients, those treated with teprotumumab were significantly more likely to achieve a proptosis reduction of at least 2 mm from baseline in the study eye after 24 weeks compared with placebo (OR 8.86, 95% CI 3.29-23.8).

With similarly positive findings reported in the second study presented earlier this year at the American Association of Clinical Endocrinologists (AACE) annual meeting, 83% of patients treated with teprotumumab achieved a reduction of 2 mm or more in proptosis compared with only 9.5% who received placebo (difference 73.45 percentage points, 95% CI 58.89-88.01).

"I think one of the exciting aspects is that [with] this drug, the effect is relatively similar to what I'm achieving with surgery," the study's lead investigator, Raymond Douglas, MD, PhD, of Cedars Sinai Medical Center in Los Angeles, previously told MedPage Today, calling the benefit "really significant, and clinically significant."

However, a quarter of patients who were treated with teprotumumab in the clinical studies experienced muscle spasms -- the most commonly reported treatment-emergent adverse event, though how the drug might cause it is unknown.

"Physician labeling could include Warning/Precaution of the possibility of teprotumumab being associated with muscle spasms," suggested the FDA briefing documents.

Other most commonly reported events included nausea, alopecia, diarrhea, fatigue, dyspepsia, headache, and dry skin. About 7% of patients also experienced hyperglycemia associated with the treatment, which will be one discussion topic during the meeting, particularly about whether glucose monitoring is needed after infusion.

The committee is also slated to discuss the level of concern with other treatment-emergent adverse events, including exacerbation of pre-existing inflammatory bowel disease seen in two teprotumumab-treated patients in the drug's trials.

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