Clinical trial analyses further substantiate that teprotumumab significantly improves debilitating effects of thyroid eye disease.- Horizon Therapeutics

Horizon Therapeutics plc announced integrated, pooled efficacy data from the Phase II and Phase III clinical trials of teprotumumab for the treatment of active thyroid eye disease (TED) compared to placebo . The results support prior analyses of significant reductions in inflammation, proptosis (eye bulging) and diplopia (double vision), as well as improvements in quality of life (QoL). These data were presented at the 89th Annual Meeting of the American Thyroid Association (ATA). This is the first presentation of the pooled analyses and builds on the individual positive results of the Phase II and Phase III clinical studies.

The pooled analysis of the Phase II (NCT01868997) and Phase III OPTIC (NCT03298867) studies presented during ATA represent the experience of 171 patients with recent onset of TED (less than nine months) treated with teprotumumab or placebo every three weeks for a total of eight infusions.

Key study findings include the following : Proptosis: At Week 24, 77.4% of patients receiving teprotumumab experienced a grater than 2 mm reduction in proptosis, compared to 14.9% of patients receiving placebo (p<0.001). the reduction in average change from baseline through week 24 in proptosis was greater in patients who received teprotumumab -2.63 mm than in those who received placebo -0.31 mm p><0.001). diplopia: the diplopia responder rate which is defined as the percentage of patients whose diplopia improved 1 or more grades was higher with teprotumumab 69.7 versus placebo 30.5 p><0.001) in those with baseline diplopia. quality of life: patients treated with teprotumumab experienced improvements in average change from baseline through week 24 in qol scores overall 15.55 vs 5.92 p><0.001), including visual functioning 16.81 vs 6.10 p><0.001) and appearance 13.51 vs 5.78 p="0.002)." the go-qol scale consists of two subscales to evaluate the quality of life of patients with ted graves ophthalmology including impacts on visual function and self-assessment of appearance. a change of 6 points is considered clinically significant. clinical activity score cas: at week 24 nearly two-thirds of teprotumumab-treated patients 61.9 had no or minimal inflammatory symptoms as measured by cas described as a cas of 0 or 1 compared to 21.8 of placebo-treated patients 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 signs or symptoms of inflammation.>

In addition, 73.8% of teprotumumab patients versus 13.8% of placebo patients had an overall response at Week 24 � defined as the percent of patients with greater than 2-point reduction in CAS and greater than 2 mm reduction in proptosis from baseline.

As previously reported, the majority of adverse events experienced with teprotumumab treatment were graded as mild to moderate and were managed in the trials, with few discontinuations. In the Phase II clinical study, the only drug-related adverse event identified by the investigators was hyperglycemia. Other adverse events included nausea, diarrhea, muscle spasms, hearing impairment and inflammatory bowel disease in a patient with a recent diagnosis of ileitis and colitis. No deaths occurred during the trial. The safety profile of teprotumumab in the Phase III clinical study was similar to that seen in the Phase II study with no new safety observations.

Comment: Teprotumumab has received Priority Review, Orphan Drug, Fast Track and Breakthrough Therapy designations from the FDA. The clinical development program for teprotumumab in the treatment of TED includes positive results from the Phase III OPTIC confirmatory clinical trial as well as positive Phase II results, which were published in The New England Journal of Medicine. .