New study holds promise for patients with LCA

A new study led by Dr. Robert Koenekoop at the Montreal Children's Hospital at the McGill University Health Centre holds promise for certain patients with Leber congenital amaurosis (LCA), an inherited retinal degenerative disease that causes significant vision loss from birth. The study, sponsored by Canadian company QLT Inc., is designed to treat patients with LCA due to genetic mutations in either retinal pigment epithelium protein 65 (RPE65) or lecithin:retinol acyltransferase (LRAT). It is the first oral medication being tested to restore sight to a specific genetic group of LCA patients. The children and adults involved were genotyped, thanks to a technique developed with funding support from the Foundation Fighting Blindness - Canada.

Positive signs come from early results in the first three patients enrolled in a Phase 1b trial, which tests QLT091001, an oral synthetic retinoid compound to treat LCA. The compound is a replacement for 11-cis-retinal, a key biochemical component of visual function which is missing in these LCA patients due to their mutations.

"These preliminary results are very exciting, are better than expected, and provide a measure of hope that a treatment might be developed for this devastating disease. We are intent on continuing the trial and undertaking further research into the safety and efficacy of this compound," said Dr. Robert Koenekoop, Principal Investigator and Director of the McGill Ocular Genetics Laboratory and Chief of Pediatric Ophthalmology at the Montreal Children's Hospital, who recently shared this data at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.

The Phase 1b trial is a short-term, open-label, proof of concept, single-center study to evaluate the safety and the effects on retinal function in 8 patients (aged 5 years and up) diagnosed with LCA due to inherited deficiency of RPE65 or LRAT. Patients received daily oral doses of QLT091001 for 7 days at the Montreal Children's Hospital at the McGill University Health Centre and were monitored to ensure overall safety. Efficacy was assessed through several visual function parameters, including best-corrected visual acuity (or clearness of vision) and visual field testing.

Interim Results

Three patients, aged 10, 12, and 38 years, all of whom have the identical mutation in LRAT, received seven days of treatment with QLT091001. All of the patients experienced clinically relevant improvements in one or more visual function parameters, including best-corrected visual acuity, Goldmann visual field, and/or retinal sensitivity. Patients also reported meaningful improvements in their visual performance related to tasks of daily living. The onset of visual changes was rapid and there was progressive improvement beyond the 7 days of treatment, with some effects persisting for up to 4 months after treatment was completed. Improvements were most significant in the youngest subject, but clinically relevant changes were also noted in the one adult treated to date. The study treatment has been well-tolerated, with mild to moderate adverse events observed, including transient headache and photophobia (sensitivity to light), and transient increase in triglyceride levels. The first two events resolved within a few days of treatment and the increased triglyceride went back to the pre-study range within a week of completing the treatment.

The study is ongoing and currently enrolling additional subjects, including those who have LCA due to mutations in RPE65. The study will continue to gather longer-term follow-up data on these patients. The current trial is expected to be completed by year end. A second study is planned to evaluate dosing and longer follow-up of the same patients.

Acceptable safety and efficacy of QLT091001 remains to be established through more nonclinical and clinical testing. QLT091001 cannot be made available to patients with LCA outside of regulated clinical trials, such as the current study as it not approved by regulatory authorities such as FDA or Health Canada. For more information about the study, go to: http://clinicaltrials.gov/ct2/show/NCT01014052?term=qlt091001&rank=1

The Foundation Fighting Blindness' Role

"The three patients in this treatment trial were discovered by our new genetic techniques, developed with the help of FFB-C grants in the recent past," said Dr. Koenekoop. The FFB-C funded work allowed Dr. Koenekoop and collaborators Drs Allikmets, den Hollander and Cremers to develop, test and apply these novel techniques so that the genotyping of blind patients is rapid and accurate. "It shows that gene and mutation discovery moves patients more quickly to a treatment. Now some of those same patients are regaining vision because of a gene specific treatment," said Dr. Koenekoop.

"We are excited about the positive outcomes for these patients and are eager to see further research to improve vision," said Sharon Colle, President & CEO of The Foundation Fighting Blindness - Canada (FFB).