General Information

Tepezza (teprotumumab-trbw) is an insulin-like growth factor-1 receptor inhibitor.

Tepezza is specifically indicated for the treatment of thyroid eye disease.

Tepezza is supplied as a solution for intravenous injection administration. The recommended dose is an intravenous infusion of 10 mg/kg for the initial dose followed by an intravenous infusion of 20 mg/kg every three weeks for 7 additional infusions.  

Mechanism of Action

Teprotumumab-trbw’s mechanism of action in patients with Thyroid Eye Disease has not been fully characterized.  Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling. 

Side Effects

Adverse effects associated with the use of Tepezza may include, but are not limited to, the following:

• muscle spasm
• nausea
• alopecia
• diarrhea
• fatigue
• hyperglycemia
• hearing impairment
• dry skin
• dysgeusia
• headache

Clinical Trial Results

The FDA approval of Tepezza was based on results from a Phase 2 clinical study, as well as the Phase 3 confirmatory clinical study, OPTIC.

The phase 2 study, the results of which were published in The New England Journal of Medicine in May of 2017, was multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24.

The phase 3 OPTIC study was a randomized, double-masked, placebo-controlled, parallel-group, multicenter study enrolled 83 subjects with moderate-to-severe active TED. Significantly more patients treated with Tepezza (82.9%) had a meaningful improvement in proptosis (≥ 2 mm) as compared with placebo patients (9.5%) without deterioration in the fellow eye at Week 24.

In a related analysis of the Phase 2 and Phase 3 clinical studies, there were more patients with complete resolution of diplopia among those treated with Tepezza (53%) compared with those treated with placebo (25%). The majority of adverse events related to Tepezza included muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dry skin, dysgeusia and headache.