SAT459 Teprotumumab Pooled Efficacy From The European Study Sites Participating In The Phase 2, OPTIC (Phase 3) And OPTIC-X Pivotal Trials

Disclosure: G.J. Kahaly: Research Investigator; Self; Horizon Therapeutics plc. Q. Fu: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. R.J. Holt: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. Background: The pivotal clinical trial program for the formal approval of teprotumumab for the treatment of thyroid eye disease (TED) in the United States (US) has previously reported excellent overall results.1 These results included data from 9 unique European Union (EU) study sites. Teprotumumab is not currently approved in the EU. Here we report pooled efficacy results from the participating EU sites. Methods: Data from the EU sites in the integrated randomized, double-masked, placebo-controlled 24-week phase 2 and 3 trials and open-label OPTIC-X trial were analyzed for the primary outcome of proptosis reduction of ≥2 mm from baseline (BL). Secondary outcomes were diplopia response (a reduction from BL in diplopia of ≥1 grade [Gorman scale]), Clinical Activity Score (CAS) of 0 or 1, an Overall response (a reduction of ≥2 in CAS plus a reduction in proptosis of ≥2 mm), the least squares (LS) and mean BL change in proptosis (mm) and the LS and mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL). Tobacco exposure was controlled for using a mixed-model repeated-measures analysis with an unstructured covariance matrix. Results: In the Integrated EU phase 2 and 3 trials, a total of 35 patients were assigned to the teprotumumab group and 39 to the placebo group. Tobacco use was 44.6% compared with 13.4% in US. Months since diagnosis of Graves’ disease was longer in EU than US (48.8 vs. 26.3). Fewer EU patients had constant diplopia (grade 3) at BL than US (13.5% vs. 25.8%). At week 24, the percentage of EU patients with a proptosis response was higher with teprotumumab than with placebo (77% [27] vs. 13% [5], P