Linsitinib phase 3 ORBIT trial doses first patients for thyroid eye disease

Sling Therapeutics, Inc. announced that the first patients have been dosed in the global Phase 3 ORBIT trial to evaluate linsitinib, a late-stage, oral, small-molecule therapy for thyroid eye disease (TED). Linsitinib, inhibits the insulin-like growth factor-1 receptor (IGF-1R) in adults with moderate-to-severe active TED, according to a press release¹ issued by the company.

How linsitinib works

IGF-1R is a validated target in TED and the only target addressed by currently approved therapies. When IGF-1R is activated, it drives characteristics of TED, ie, inflammation and proptosis. Linsitinib has an established safety profile from treatment of more than 900 patients across 15 clinical trials in multiple disease areas and has received Fast Track Designation from the FDA, according to the company.

For clinicians managing TED, the treatment landscape has so far been defined by infused biologic therapy, with attendant burdens including travel to infusion centers and safety considerations such as hearing loss, hyperglycemia, and menstrual cycle changes. Linsitinib is being developed as an oral alternative targeting the same IGF-1R pathway that drives the orbital inflammation and fibrous tissue growth underlying TED. TED predominantly affects women and most frequently occurs in people with Graves'-related hyperthyroidism.

"ORBIT represents the next step toward what we believe could be a meaningful advancement in the treatment of TED," said Ryan Zeidan, PhD, President and Chief Executive Officer of Sling Therapeutics.

He continued, "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, which is an important distinction in a treatment landscape currently defined by infused biologics.”

Raymond Douglas, MD, PhD, an aesthetic and reconstructive oculoplastic surgeon in Beverly Hills, CA, noted the clinical stakes of delayed or inaccessible treatment. "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. An effective oral therapy such as linsitinib could help address these barriers and meaningfully expand access to treatment. With the proptosis responses and favorable safety profile observed with linsitinib to date, I look forward to seeing its potential further evaluated in the ORBIT trial."

The ORBIT trial is the second pivotal study of linsitinib for treating TED and will add to the totality of evidence supporting linsitinib as an effective disease-modifying therapy for TED minus the treatment burden and safety tradeoffs associated with currently available biologic options, Zeidan went on to explain.

Trial design

A total of 130 participants are expected to be enrolled in the study. They will be randomized 1:1 to oral linsitinib 150 mg or placebo twice daily for 24 weeks. The primary endpoint is the proportion of patients with a proptosis response at week 24; a response is defined as a proptosis decrease of a minimum of 2 mm in the study eye and no worsening in the fellow eye.

The secondary endpoints are the mean change from baseline in proptosis, overall responder rate, Clinical Activity Score, and the Graves' Ophthalmopathy Quality of Life questionnaire. After 24 weeks, the patients can enroll in a 24-week open-label extension (identifier: NCT07753603), according to the press release.

Reference

1. Sling Therapeutics. https://www.google.com/search?q=sling+therapeutics+announces+first+patients+doses+in+global+phase+3+orbit+pivotal+trial&rlz=1C5GCEM_en___US1146&oq=sling+therap&gs_lcrp=EgZjaHJvbWUqCAgAEEUYJxg7MggIABBFGCcYOzIGCAEQRRg5Mg0IAhAuGMcBGNEDGIAEMgcIAxAAGIAEMgcIBBAAGIAEMgcIBRAAGIAEMgYIBhBFGDwyBggHEEUYPNIBCDM4ODNqMGo3qAIAsAIA&sourceid=chrome&source=chrome.ob&ie=UTF-8