Sling Therapeutics Doses First Patients in Phase III ORBIT Trial of Oral Linsitinib for Thyroid Eye Disease
核心洞察
Sling Therapeutics (搜索) has dosed the first patients in the global Phase III ORBIT trial of oral linsitinib in moderate to severe active thyroid eye disease (搜索).
ORBIT will randomize approximately 130 adults 1:1 to linsitinib 150 mg or placebo twice daily for 24 weeks, with proptosis response at week 24 as the primary endpoint.
The Phase IIb/III LIDS trial reported positive topline results in January 2025, meeting its primary endpoint with a 52% proptosis responder rate at week 24 (p = 0.01).
Sling Therapeutics (搜索) has dosed the first patients in ORBIT, a global Phase III pivotal trial of oral linsitinib in adults with moderate to severe active thyroid eye disease (搜索) (TED), the Michigan-based clinical-stage company announced on September 16, 2026. The enrollment milestone advances the only oral small molecule in late-stage TED development into a registrational study designed to support an eventual regulatory submission.
Linsitinib is an oral small molecule inhibitor of 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.
Trial Design and Endpoints
ORBIT is a randomized, double-masked, placebo-controlled study expected to enroll approximately 130 participants, randomized 1:1 to receive 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 participants achieving a reduction of at least 2 mm in proptosis in the study eye without a corresponding worsening in the fellow eye.
Secondary endpoints include mean change from baseline in proptosis, overall responder rate, Clinical Activity Score (CAS), and the Graves' Ophthalmopathy Quality of Life (GO-QoL) questionnaire. Following the 24-week double-masked treatment period, patients will be eligible to enroll in a 24-week open-label extension. The trial is registered on clinicaltrials.gov under identifier NCT07753603.
"ORBIT represents the next step toward what we believe could be a meaningful advancement in the treatment of TED. Linsitinib has already demonstrated the potential to deliver clinically meaningful improvements in proptosis with a differentiated safety profile, and it does so as an oral therapy – an important distinction in a treatment landscape currently defined by infused biologics," said Ryan Zeidan, Ph.D., President and Chief Executive Officer of Sling Therapeutics (搜索).
Prior Phase IIb/III Data
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 the 150 mg twice-daily dose, achieving a 52% proptosis responder rate at week 24 (p = 0.01).
No drug-related hearing impairment was reported in the 150 mg arm, with a 0% placebo-adjusted tinnitus rate and a 3% rate of hyperglycemia — a safety profile that Sling said differentiates linsitinib from the hearing-related adverse events associated with intravenous IGF-1R (搜索)-targeting biologics. Elevated liver transaminases were observed but resolved without signs of drug-induced liver injury.
Positioning Against Approved and Investigational Biologics
Amgen's Tepezza (teprotumumab-trbw), the established intravenous standard of care, reported a 76.7% proptosis responder rate in a Phase III trial of a subcutaneous formulation delivered via on-body injector, positioning the reformulation as a potential alternative to infusion-center visits. Viridian Therapeutics (Nasdaq: VRDN) received FDA approval for its Lumvoa (veligrotug-vvze (搜索)) in June 2026, supported by two pivotal Phase III trials, and its subcutaneous anti-IGF-1R (搜索) antibody elegrobart (搜索) met its primary endpoint in a Phase III chronic TED trial earlier this year, with a Biologics License Application submission targeted for Q1 2027.
Sling's commercial argument rests on route of administration and tolerability rather than efficacy magnitude. The current approved TED regimen requires eight IV infusions over 24 weeks, with documented risks of hearing impairment and hyperglycemia. An effective twice-daily oral therapy with a cleaner safety profile could expand prescriber access beyond specialist infusion centers, particularly for patients who decline or cannot access biologic infusions.
"TED is a serious ocular autoimmune disease that can progress rapidly, cause permanent damage and, in severe cases, threaten vision. Early treatment is critical, yet many patients remain untreated due to limitations of currently available therapies, including concerns about long-term hearing loss and the burden of traveling to infusion centers," said Raymond Douglas, M.D., Ph.D., board-certified aesthetic and reconstructive oculoplastic surgeon. "An effective oral therapy such as linsitinib could help address these barriers and meaningfully expand access to treatment."
Sling holds FDA Fast Track Designation for linsitinib and has appointed a Chief Commercial Officer as it prepares for a potential regulatory filing.