QLT Announces Positive Final Results From Phase 1b Retreatment Trial With Oral Synthetic cis-Retinoid In Subjects With LCA Or RP Due To Mutations In RPE65 Or LRAT

QLT Inc. QLTI QLT ("QLT" or the "Company") today announced positive final results from its international, multi-center, Phase 1b clinical trial of repeated treatments of oral QLT091001 in subjects with Leber Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP) due to inherited genetic mutations in retinal pigment epithelium (RPE65) or lecithin:retinol acyltransferase (LRAT). The results, which confirm the top line efficacy and safety outcomes reported from the study in February 2014, will be presented tomorrow, September 13, 2014, at the 47th Annual Scientific Meeting of The Retina Society in Philadelphia, PA, by Dr. Hendrik Scholl, the Dr. Frieda Derdeyn Bambas Professor of Ophthalmology and Director of the Visual Neurophysiology Service at the Wilmer Eye Institute at the Johns Hopkins Hospital, and an investigator in the trial. The presentation slides will be made available on QLT's web site following the Retina Society Meeting. "As a follow up study to QLT's RET IRD 01 study, for which the LCA data were recently published in The Lancet, it is encouraging to observe clinically meaningful improvements in visual fields with repeated dosing of QLT091001 in both LCA and RP patients with RPE65 or LRAT mutations," said Dr. Scholl. "Also, there appears to be a small, but positive effect on visual acuity in both patient groups. This is promising given the relatively long duration of this study and the fact that inherited retinal disease is characterized by a progressive loss of visual function." This multicenter, open-label Phase 1b retreatment trial was an extension study in which LCA or RP subjects with RPE65 or LRAT mutations who had been treated with a single course of QLT091001 in the Company's previously completed Phase 1b study, received up to three 7-day courses of QLT091001 to assess visual outcomes and safety following retreatment. Subjects received treatment with QLT091001 at doses of 10, 40 or 60 mg/m2, with the majority of subjects receiving 40 mg/m2. Visual fields were assessed using Goldmann visual field (GVF) and visual acuity was assessed using best-corrected visual acuity (BCVA) at baseline and days 7, 14, 30 and 60 after each treatment course, then bimonthly until the next treatment course. Results of the final analysis confirmed the response rates previously reported in February 2014, with 19 of 27 subjects (70%) having a visual field response (increase in retinal area of at least 20% from the study baseline at 2 consecutive visits starting within 6 months of any study treatment), and 19 of 27 subjects (70%) having a visual acuity response (increase of at least 5 letters at 2 consecutive visits starting within 6 months of any study treatment) (see primary isopter rates and visual acuity rates in Table below). Over the course of the entire study spanning multiple treatment courses, these responses were durable, with the visual field response lasting an average of 235 days (Min-Max = 7 – 742 days), and the visual acuity response lasting an average of 232 days (Min-Max = 7 – 616 days). Overall, 10 of 13 LCA subjects (77%), and 12 of 14 RP subjects (86%) were classified as responders for either visual field retinal area or visual acuity. Table: Results for Goldmann Visual Field and Visual Acuity Responders Number (%) of Subjects RP N=14 LCA N=13 All N=27 Goldmann Visual Field Primary isopter ≥ 20% Increase At least one eye 12 (86%) 7 (54%) 19 (70%) Both eyes 11 (79%) 7 (54%) 18 (67%) ≥ 40% Increase At least one eye 9 (64%) 6 (46%) 15 (56%) Both eyes 5 (36%) 5 (38%) 10 (37%) Any isopter * ≥ 20% Increase At least one eye 12 (86%) 12 (92%) 24 (89%) Both eyes 11 (79%) 11 (85%) 22 (81%) ≥ 40% Increase At least one eye 9 (64%) 9 (69%) 18 (67%) Both eyes 8 (57%) 7 (54%) 15 (56%) Visual Acuity ≥ 5 Letter Increase At least one eye 9 (64%) 10 (77%) 19 (70%) Both eyes 1 (7%) 3 (23%) 4 (15%) GVF response: ≥20% change or ≥40% change in retinal area from baseline at 2 consecutive visits in at least 1 eye within 6 months of any treatment. VA response: ≥ 5 letter increase from baseline at 2 consecutive visits in at least 1 eye within 6 months of any treatment. * Since an improvement in vision can result from an increase in visual field for other isopters and not just the primary isopter (one with a mid-range retinal area less prone to floor and ceiling effects and chosen for each individual subject), changes in GVFs were also assessed at a number of additional isopters. Repeated treatment with up to three courses of QLT091001 was generally well tolerated. Adverse events were consistent with the retinoid class of medications and with the previously completed Phase 1b single course of treatment study (RET IRD 01) and were transient and/or reversible. Headache and fatigue were the most common treatment-related adverse events followed by erythema, nausea, photophobia, photopsia, flushing and vomiting. Reversible elevations in triglyceride, LDL, cholesterol, AST and ALT levels and reduction in HDL and thyroxine were recorded. Most treatment-related adverse events were either mild (78%) or moderate (18%) in intensity. One serious adverse drug reaction (pseudotumor cerebri or intracranial hypertension, a known class effect of retinoids) was reported in the study and it was resolved. The incidence of treatment-related adverse events did not increase with successive treatment courses.