Sling Therapeutics Initiates Phase III Trial of Linsitinib in Thyroid Eye Disease
核心洞察
Sling Therapeutics (搜索) has dosed the first patients in ORBIT, a global Phase III trial of oral linsitinib in moderate to severe active thyroid eye disease (搜索).
The randomized, double-masked, placebo-controlled study will enroll about 130 adults receiving linsitinib 150 mg or placebo twice daily for 24 weeks.
The primary endpoint is proptosis responder rate at week 24, following positive Phase IIb/III LIDS results reported in January 2025.
Michigan-based Sling Therapeutics (搜索) has dosed the first patients in the ORBIT pivotal trial, a global Phase III study of linsitinib in moderate to severe active thyroid eye disease (搜索) (TED). The enrollment milestone moves the only oral small molecule in late-stage TED development into a registrational study designed to support an eventual regulatory submission.
Linsitinib inhibits the insulin-like growth factor-1 receptor (IGF-1R (搜索)) and the insulin receptor, blocking downstream signaling that drives orbital fibroblast activation, inflammation, and the proptosis characteristic of TED. ORBIT is randomized, double-masked, and placebo-controlled, enrolling approximately 130 adults 1:1 to oral linsitinib 150 mg or placebo twice daily for 24 weeks. The primary endpoint is the proportion of proptosis responders at week 24, defined as a reduction of at least 2 mm in the study eye without corresponding worsening in the fellow eye; secondary endpoints include mean proptosis change, overall responder rate, Clinical Activity Score, and the Graves' Ophthalmopathy Quality of Life questionnaire. Patients completing the double-masked period may enter a 24-week open-label extension.
ORBIT is the second pivotal study of linsitinib in TED. The Phase IIb/III LIDS trial reported positive topline results in January 2025, meeting its primary endpoint with statistical significance at 150 mg twice daily and a 52% proptosis responder rate at week 24 (p = 0.01). No drug-related hearing impairment was reported in that arm, with a 0% placebo-adjusted tinnitus rate and 3% hyperglycemia; elevated liver transaminases resolved without signs of drug-induced liver injury. Sling holds FDA Fast Track Designation for linsitinib and has appointed a Chief Commercial Officer as it prepares for a potential regulatory filing, arguing its commercial case on route of administration and tolerability rather than efficacy magnitude.
Source: Sling starts Phase III trial of oral TED therapeutic linsitinib - AllSci