OR27-04 Efficacy And Safety Results From The Randomized, Placebo-controlled Multicenter Trial With Teprotumumab In Chronic-Low Clinical Activity Score Thyroid Eye Disease Patients
Authors: Douglas Raymond S , Couch Steven , Wester Sara T , Fowler Brian T , Liu Catherine , Subramanian Prem , Tang Rosa , Nguyen Quang T , Maamari Robi N , Hsu Kate , Karon Michael , Stan Marius 
Published: October 2023

Disclosure: R.S. Douglas: Consulting Fee; Self; Horizon, Immunovant, Viridian. Research Investigator; Self; Horizon. S. Couch: Research Investigator; Self; Horizon. S.T. Wester: Advisory Board Member; Self; Horizon. Consulting Fee; Self; Immunovant, Sling. Research Investigator; Self; Horizon. B.T. Fowler: Consulting Fee; Self; Horizon. Research Investigator; Self; Horizon. C. Liu: Research Investigator; Self; Horizon. Other; Self; Royalties from Wolters-Kluwer. P. Subramanian: Consulting Fee; Self; Horizon, Gensight, Viridian. Research Investigator; Self; Horizon. R. Tang: Consulting Fee; Self; Viridian, Alexion, Valenza. Research Investigator; Self; Horizon, Viridian, Novartis, Immunovant, Vasaragen. Speaker; Self; Serono Journal Club. Q.T. Nguyen: Research Investigator; Self; Horizon. R.N. Maamari: Research Investigator; Self; Horizon. K. Hsu: Employee; Self; Horizon. Stock Owner; Self; Horizon. M. Karon: Employee; Self; Horizon. Stock Owner; Self; Horizon. M. Stan: Consulting Fee; Self; Septerna Inc, Third Rock Ventures LLC, Genentech, MedicXi Ventures, ArgenX US Inc, Tourmaline Bio, Lassen Therapeutics, Ortho Clinical Diagnostics, Siemens Healthcare, Tolmar Inc, OSE, Immunotherapeutics, Roivant Sciences. Research Investigator; Self; Horizon, Immunovant, ValenzaBio, Sling Therapeutics.

Background: Early inflammatory thyroid eye disease (TED) gives way to chronic disease which may lead to long-term disfiguring proptosis (eye-bulging). Teprotumumab, an IGF-1 receptor inhibitor, significantly improved signs and symptoms of newly diagnosed TED (6-13 months) with active disease (clinical activity score [CAS] ≥4) in prior studies. We present data from the first randomized, placebo (PBO)-controlled trial (NCT04583735) with teprotumumab in chronic/low CAS TED, where disease has not regressed.

Methods: Pts met all following criteria: ≥18 yrs, TED 2-10 yrs, inactive disease or &gt;1 yr without progression in proptosis/diplopia/new symptoms, baseline (BL) CAS≤1, increased proptosis ≥3mm before TED or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab and no steroids within 3 wks of screen. Pts received teprotumumab or PBO once every 3 wks for 21 wks. Primary endpoint was improvement in proptosis(mm) from BL at Wk 24 vs PBO. Secondarily proptosis responders (≥2mm improvement), diplopia responders (≥1 grade improvement on Gorman scale 0-3) with resolved diplopia (grade 0) and improvement in Graves’ Ophthalmopathy-QoL (GO-QoL) visual function (VF) and appearance (AP) subscales were assessed. Treatment-emergent adverse events (TEAE) and AEs of special interest are reported. Study was solely sized/powered for proptosis.

Results: 62 pts were randomized 2:1 (ITT, teprotumumab:42; PBO:20), 80.6% were female, mean(SD) age was 48.7(14.94) yrs. Mean(SD) TED duration was 5.2(1.8) yrs. 87.1% were never/former smokers. At BL, mean(SD) proptosis was 24.4(2.94) mm, mean CAS was 0.4, and 29% (teprotumumab, n=14, PBO, n=4) had diplopia with a mean score ∼2. 93%(39) of teprotumumab pts completed the study. At Wk 24, proptosis improvements from BL were significantly greater in the teprotumumab group [2.41 (0.228) mm] vs PBO [0.92(0.323) mm], P&lt;.001. Proptosis response was observed in 26/42 (62%) of teprotumumab pts vs 5/20 (25%) of PBO, P=.01. Diplopia improvement was observed in 6/14 (43%) teprotumumab pts with resolved diplopia in 4(29%) vs 2/4(50%) in PBO and 1(25%) resolved. Significantly greater improvement from BL was observed on GO-QoL-VF for teprotumumab (8.73) vs PBO (2.41), P=.03. Change from BL on AP was 10.03 vs 7.19, P= .65. TEAEs proportions were similar: 33/41(80.5%) of teprotumumab, and 16/20(80%) of PBO pts. Hyperglycemia was reported in 6(15%) vs 2(10%) and hearing impairment in 9(22%) vs 2(10%), respectively. There were two AE discontinuations: teprotumumab (left ear conductive hearing loss with congenital anomaly) and PBO (infusion related).

Conclusions: For the first time in pts with longstanding TED and low CAS/inflammation, a medical therapy, teprotumumab, produced significant improvement in proptosis as compared with PBO supporting its use regardless of TED duration or activity. The safety profile was comparable to that previously reported.

Presentation: Saturday, June 17, 2023