Vision Improvement After Retreatment with an Oral Synthetic cis-Retinoid (QLT091001) in Subjects with LCA or RP due to Mutations in RPE65 or LRAT

Abstract

 

Purpose

 

To assess the visual outcomes and safety of retreatment with oral 9-cis-retinyl acetate (QLT091001) in subjects with LCA (Leber congenital amaurosis) or RP (retinitis pigmentosa) due to mutations in RPE65 or LRAT.

 

Methods

 

In a multi-center, open-label Phase Ib study, 27 subjects who had received one 7-day course of QLT091001 in an earlier study received up to three 7-day courses of QLT091001 at doses of 10, 40 (majority of subjects) or 60 mg/m² with a minimum of 4 weeks between treatment courses. Goldmann visual field (GVF) and best-corrected visual acuity (BCVA) were assessed at baseline and days 7, 14, 30, and 60 after each treatment course and then bimonthly until the next treatment course. Safety assessments included complete ophthalmic and physical examination, ERG, OCT, ECG, laboratory testing and reported adverse events.

 

Results

 

19 of 27 subjects (70%) had a GVF response (increase in functional retinal area of at least 20% from the study baseline at a minimum of 2 consecutive visits starting within 6 months of any study treatment), and 19 of 27 subjects (70%) had a visual acuity response (increase of at least 5 letters at a minimum of 2 consecutive visits starting within 6 months of any study treatment) (Fig). Over the course of the entire study, spanning multiple treatment courses, the GVF and visual acuity responses were durable (average of 235 days, range: 7 - 742 days, and 232 days, range: 7 - 616 days, respectively). Overall, 10 of 13 LCA subjects (77%), and 12 of 14 RP subjects (86%) were classified as responders for either functional retinal area or visual acuity. Headache, fatigue, photophobia, photopsia, erythema, flushing, nausea and vomiting were reported and reversible elevations in triglyceride, LDL, cholesterol, AST and ALT levels and reduction in HDL and thyroxine were recorded. AEs were transient and/or reversible and were consistent with the retinoid class of compounds. One SAE (intracranial hypertension, a known class effect of retinoids) was reported in the study and it was resolved. The incidence of treatment-related AEs did not increase with successive treatment courses.

 

Conclusions

 

Repeated treatments with QLT091001 led to sustained visual improvements in a large subset of LCA or RP subjects with mutations in either RPE65 or LRAT.