June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Vision Improvement After Retreatment with an Oral Synthetic cis-Retinoid (QLT091001) in Subjects with LCA or RP due to Mutations in RPE65 or LRAT
Author Affiliations & Notes
  • Hendrik P Scholl
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD
  • Robert K Koenekoop
    Montreal Children's Hospital, Montreal, QC, Canada
  • Anthony T Moore
    Institute of Ophthalmology, University College London, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Eberhart Zrenner
    Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany
  • L Ingeborgh Van Den Born
    Rotterdam Eye Hospital and Ophthalmic Institute, Rotterdam, Netherlands
  • Gerald A Fishman
    Pangere Center for Inherited Retinal Diseases, Chicago Lighthouse, Chicago, IL
  • Gislin Dagnelie
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD
  • Ronald A Schuchard
    Stanford University School of Medicine, Palo Alto, CA
  • David A Saperstein
    Vitreoretinal Associates of Washington, Seattle, WA
    QLT Inc., Vancouver, BC, Canada
  • Sushanta Mallick
    QLT Inc., Vancouver, BC, Canada
  • Footnotes
    Commercial Relationships Hendrik Scholl, QLT Inc. (F); Robert Koenekoop, None; Anthony Moore, QLT Inc. (C); Eberhart Zrenner, QLT Inc. (C), QLT Inc. (R); L Van Den Born, None; Gerald Fishman, None; Gislin Dagnelie, QLT Inc. (F); Ronald Schuchard, QLT Inc. (C); David Saperstein, QLT Inc. (C), Retinagenix LLC (I), Retinagenix LLC (P); Sushanta Mallick, QLT Inc. (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1285. doi:
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      Hendrik P Scholl, Robert K Koenekoop, Anthony T Moore, Eberhart Zrenner, L Ingeborgh Van Den Born, Gerald A Fishman, Gislin Dagnelie, Ronald A Schuchard, David A Saperstein, Sushanta Mallick, ; Vision Improvement After Retreatment with an Oral Synthetic cis-Retinoid (QLT091001) in Subjects with LCA or RP due to Mutations in RPE65 or LRAT. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1285.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.  

 
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