Phase III OPTIC clinical trial evaluating Tepezza for thyroid eye disease is published in NEJM.- Horizon Therapeutics

Horizon Therapeutics plc announced that The New England Journal of Medicine has published comprehensive results of the Phase III OPTIC clinical trial evaluating Tepezza (teprotumumab-trbw) for Thyroid Eye Disease (TED). OPTIC is part of the largest clinical program in TED and demonstrates that Tepezza provides significant improvements in proptosis (eye bulging) and diplopia (double vision) compared to placebo. Key trial findings published in The New England Journal of Medicine include the following: Proptosis : At Week 24, more patients receiving Tepezza (83%) versus placebo (10%) had a greater than 2 mm reduction of proptosis in the study eye, without deterioration in the fellow eye (p<0.001). mean change in proptosis with tepezza was ?3.32 mm at week 24, which is similar to the results attained on average with orbital decompression surgery. all patients who received tepezza had some reduction in proptosis at week 24, regardless of the initial severity of proptosis, which ranged from 16 mm to 31 mm in the trial. the number needed-to-treat (nnt) was 1.36 (nnt is the number of patients needed to treat in order to achieve response in one additional patient). muscle and fat volume : orbital imaging was performed at one trial site, as a part of the site’s standard practice, and showed that the reduction in proptosis was associated with a reduction in extraocular muscle volume, orbital fat volume or both. all six patients in the tepezza group had significantly decreased extraocular muscle volume in the study eye, with an average percentage decrease of 35%. orbital fat volume in the study eye had an average percentage decrease of 17%. orbital fat volume was reduced by 44% in one patient and by 40% in another. diplopia : at week 24, 68% of patients receiving tepezza had an improvement from baseline of at least one grade in diplopia, compared to 29% of patients receiving placebo (p="0.001)." this endpoint measured the percentage of patients who reported at least some diplopia at baseline in the study eye and who had a reduction of greater than 1 grade with no corresponding deterioration ( greater than 1 grade worsening) in the fellow eye at week 24. quality of life (qol) : at week 24, patients receiving tepezza had a mean change of 17 on the graves' ophthalmopathy quality of life (go-qol) scale compared with a change of 2 for patients receiving placebo (p><0.001). these scores indicate a statistically and clinically meaningful improvement over placebo in these qol measures. the go-qol scale consists of two subscales to evaluate the quality of life of ted (graves’ ophthalmology) patients, including impact on visual function and self-assessment of appearance. a change of 6 points is considered clinically significant. clinical activity score (cas) : at week 24, more patients achieved a cas value of 0 or 1 with tepezza treatment (59% vs 21% of placebo participants) (p><0.001). cas is a scale used to assess the disease activity of ted, and measures the degree of inflammation, including pain, swelling and redness. the cas scale ranges from 0 to 7, with a score of 0 representing no swelling or activity. overall responder rate : at week 24, patients treated with tepezza had an overall responder rate of 78% compared with 7% in the placebo group (p><0.001). overall responder rate is the percent of participants with a greater than 2-point reduction in cas and a greater than 2 mm reduction in proptosis from baseline, without deterioration in the fellow eye. in general, the onset of activity of tepezza was rapid and evident at the first post-baseline assessment at week 6, with continued improvement over the full 24-week course of treatment. the majority of adverse events experienced with tepezza treatment were graded as mild to moderate and were managed in the trial, with few discontinuations. adverse events ( greater than 10%) included muscle spasm, alopecia, nausea and fatigue. adverse events of special interest that occurred in 5% of patients or less within 21 days after the last dose included two patients in the tepezza group who experienced hyperglycemia (both cases were mild) and five patients in the tepezza group who experienced hearing impairment (all cases resolved). no deaths occurred. two serious adverse events occurred in the tepezza group: pneumothorax (probably unrelated to the study drug, as determined by an investigator) and an infusion reaction that led to withdrawal from the trial. see: douglas, et al. teprotumumab for the treatment of active thyroid eye disease. n engl j med. 2020;382(4):341-352.>