New Oral Medication Shows Significant Progress in Restoring Vision to Patients with Leber Congenital Amaurosis (LCA)

QLT Inc announced the publication of data from its Phase 1b proof-of-concept trial of QLT091001 in patients with Leber congenital amaurosis (LCA) due to inherited genetic mutations in RPE65 or LRAT genes. In the study, treatment for seven days with oral QLT091001 demonstrated a restoration of clinically meaningful visual function in 11 of the 14 LCA patients, as measured by improvement in Goldmann Visual Fields (GVF) or visual acuity. Self-reported or parent-reported improvements in activities of daily living supported these findings.

“Currently, children and adults with LCA due to these genetic mutations progressively lose vision, eventually becoming totally blind as there are no proven therapies that either slow or reverse their condition,” stated David A. Saperstein, M.D., a retina physician who serves as Chief Medical Advisor to QLT and is a co-author of the Lancet paper. “The results of this trial are quite promising. If borne out in further clinical trials, QLT091001 would have the potential to become the first oral medication to improve vision and quality of life in patients with these forms of LCA.”

The trial enrolled 14 patients, ages 6–38, with Leber congenital amaurosis due to mutations in RPE65 or LRAT. Patients received seven days of oral QLT091001 (12 subjects received 40mg/m2 per day and two subjects received 10mg/m2 per day). Patients were assessed at baseline and days 7, 9, 14, and 30, and every two months thereafter, for up to three years, for safety outcomes and visual function endpoints, which included GVF, visual acuity, and a functional MRI assessment.

In the study, 10 of 14 patients had an improvement of GVF, with a mean increase in retinal area of 28–683%. Six patients had an improvement in visual acuity, with a mean increase of 2–30 letters. After two years, three patients had a sustained GVF response and four had a sustained visual acuity response. Four patients had functional MRI scans, which correlated with visual response or absence of response to treatment. Ten of the responders had self-reported improvements in activities of daily living.

No serious adverse events occurred, although transient headaches, photophobia, reduction in serum HDL concentrations, and mild, reversible increases in serum triglycerides and aspartate aminotransferase concentrations were observed.

“This is the first time that an oral drug has improved the visual function of blind patients with LCA,” says the study’s lead author, Dr Robert Koenekoop, Professor of Human Genetics, Paediatric Surgery and Ophthalmology at McGill University in Montreal. “By giving patients with RPE65 or LRAT mutations an oral retinoid intermediate (QLT091001) most patients’ vision improved rapidly. We discovered that a certain portion of the retinal cells that were not working because of the lack of 11-cis retinal could be woken up,” explains Dr Koenekoop. “Contrary to what was previously thought, children with LCA and defects in RPE65 or LRAT are not born with dead retinal cells; the cells can simply go dormant, and they can remain dormant for years before they eventually die. The oral drug we tested awakened these cells and allowed patients to see” said Dr Koenekoop.

Fighting Blindness Research Manager Maria Meehan commented on the findings saying: “This revolutionary oral drug has been shown to be safe and well tolerated while rapidly restoring some vision in this initial trial. We look forward to seeing further data from this trial and welcoming this new era of therapies for retinal degenerative diseases”.

About Leber Congenital Amaurosis (LCA)

LCA is an inherited degenerative retinal disease characterised by abnormalities such as roving eye movements and sensitivity to light, and manifesting in severe vision loss from birth. Both rod and cone photoreceptors are affected in LCA. Eye examinations of infants with LCA reveal normal appearing retinas. However, a low level of retinal activity, measured by electroretinography, indicates very little visual function. According to current epidemiological estimates, LCA affects approximately one in 81,000 new-borns worldwide, of which approximately 10% carry the inherited deficiencies of either RPE65 or LRAT.

For more information about LCA research please click here or contact Fighting Blindness Research Manager Maria Meehan on 01 6789 004 or