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Safety and Biodistribution of Topical Laquinimod, an Immunomodulator Targeting Aryl Hydrocarbon Receptor: The LION Study

Year: 2026

Type: article

Abstract: Purpose: To evaluate the safety, tolerability, and distribution of laquinimod (LAQ) eye drops as a potential steroid-sparing anti-inflammatory therapy. Design: Phase I clinical trial conducted at the Byers Eye Institute, Stanford University. NCT06161415. Participants: Patients scheduled for elective pars plana vitrectomy for various noninfectious indications. Methods: Enrolled subjects were instructed on proper LAQ storage and administration and received the drops for 14 days prior to surgery. Patients were sequentially assigned into 3 groups receiving daily LAQ doses of 0.6, 1.2, and 1.8 mg, with dose escalation permitted only in the absence of safety concerns in the preceding cohort. A preoperative visit was performed following 7 days of LAQ administration. On the day of surgery, aqueous, vitreous, and plasma samples were collected for LAQ quantification. Two postoperative follow-up visits were conducted. Main Outcome Measures: Tolerability; safety of the LAQ eye drop, assessed via ophthalmic examination, multimodal imaging, laboratory tests, and electrocardiogram; and LAQ concentrations in aqueous, vitreous, and plasma. Results: Ten participants completed the 14-day topical LAQ and all study visits, except one where pars plana vitrectomy was canceled; however, subject completed LAQ course and safety follow-up. The mean age was 59.9 ± 15 years, with a female predominance (70%). Given there were no dose-limiting toxicities, participants sequentially received daily doses of 0.6 mg (n = 4), 1.2 mg (n = 3), and 1.8 mg (n = 3). Following the exclusion of insufficient samples, LAQ levels were analyzed in 8 vitreous and 7 aqueous specimens. Laquinimod was well tolerated at all doses, with 3 adverse events unrelated to the study drug. Laquinimod was detected in aqueous, vitreous, and plasma with dose-dependent levels across all doses. Mean total LAQ level was significantly higher in aqueous rising from 508.5 to 3640.0 ng/mL, exceeding vitreous levels that rose from 6.89 to 38.50 ng/mL. Notably, unbound LAQ levels remained significant. Plasma concentrations remain within established safety ranges, with mean LAQ levels increasing from 153.4 to 563.5 ng/mL. Conclusions: Topical LAQ was safe and well tolerated at daily doses of 0.6, 1.2, and 1.8 mg, with measurable penetration into the posterior segment. Dose-dependent drug levels were detected in vitreous, aqueous, and plasma. These findings support investigation of LAQ's therapeutic potential for inflammatory eye diseases. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Source: Ophthalmology Science

DOI: 10.1016/j.xops.2026.101186