QLT Inc. Announces Positive Interim Results From Phase 1b Study of its Oral Synthetic Retinoid Compound in Leber Congenital
VANCOUVER, British Columbia, April 20, 2010 (GLOBE NEWSWIRE) -- QLT Inc. (Nasdaq:QLTI) (TSX:QLT) ("QLT" or the "Company") today announced interim results from the first 3 subjects enrolled in a Phase 1b clinical proof-of-concept study of QLT091001 in the treatment of Leber congenital amaurosis (LCA), an inherited progressive retinal degenerative disease that leads to retinal dysfunction and significant visual impairment beginning at birth. QLT091001 is an orally administered synthetic retinoid replacement for 11-cis-retinal, which is a key biochemical component of visual function. The Phase 1b trial is a short-term, open-label, single-center study to evaluate the safety profile and effects on retinal function in 8 pediatric subjects (aged 5 to 14 years) diagnosed with LCA due to inherited deficiency of retinal pigment epithelium protein 65 (RPE65) or lecithin:retinol acyltransferase (LRAT). Based on the positive results from the first 2 pediatric patients, a protocol exception was granted to also treat an adult patient. Subjects receive daily oral doses of QLT091001 for 7 days at the Montreal Children's Hospital at the McGill University Health Centre, Montreal, Canada under the supervision of the trial's principal investigator, Robert K. Koenekoop, M.D., Ph.D. Patients were monitored to ensure overall safety. Efficacy assessments included several visual function parameters including best-corrected visual acuity and visual field testing. Interim Results Three subjects aged 10, 12, and 38 years, all of whom have a genetic mutation in LRAT, have been enrolled and treated to date. After 7 days of treatment with QLT091001, all of the subjects experienced clinically relevant improvements in one or more visual function parameters, including best-corrected visual acuity, Goldmann visual field, and/or retinal sensitivity as measured by full-field sensitivity threshold testing. Subjects have 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 pronounced in the youngest subject, but clinically relevant changes were also noted in the one adult subject treated to date. The study treatment has been well-tolerated, with mild to moderate adverse events observed including transient headache and photophobia, and an increase in triglyceride levels. The study is ongoing and will enroll additional subjects, including those who have LCA due to mutations in RPE65. Because of the prolonged treatment effects, the study will also continue to gather longer-term follow-up data on these subjects. Completion of the current trial is expected before year end. The results from the first 3 subjects will be introduced and discussed by Dr. Koenekoop in a previously scheduled mini-symposium entitled, "An Overview of Retinal Dystrophies: from Gene Discoveries to New Therapies" at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Fort Lauderdale, Florida on May 3, 2010 at 3:45 p.m. (Eastern Time). "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. Koenekoop, Director of the McGill Ocular Genetics Laboratory and Chief of Pediatric Ophthalmology at Montreal Children's Hospital. "We look forward to sharing these data with the ophthalmology community beginning at ARVO in early May." "We are very excited about the positive outcomes for these patients and are eager to complete patient enrollment," said Bob Butchofsky, President and Chief Executive Officer of QLT. While these early results are promising, the safety and efficacy of QLT091001 remains to be fully evaluated through additional preclinical and clinical testing. QLT091001 cannot be made available to patients with LCA outside of regulated clinical trials, such as the current study. About Leber Congenital Amaurosis (LCA) LCA is an inherited degenerative retinal disease characterized by abnormalities such as roving eye movements and sensitivity to light, and manifesting in severe vision loss from birth. 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. Approximately 1 child out of every 81,000 births will inherit the disease. Mutations in the genes for retinal pigment epithelium protein 65 (RPE65) and lecithin:retinol acyltransferase (LRAT) result in an inadequate production of 11-cis-retinal and occur in approximately 10% of patients with LCA and to a lesser extent in retinitis pigmentosa (RP), another inherited retinal dystrophy. About Synthetic Retinoid Drugs Genetic diseases in the eye such as LCA and RP arise from gene mutations of enzymes or proteins required in the biochemistry of vision. QLT091001 is a replacement for 11-cis-retinal, which is an essential component of the retinoid-rhodopsin cycle and visual function. The basis for using synthetic retinoids as replacement therapy for conditions where genetic defects result in deficiency of 11-cis-retinal is founded on experiments in mouse genetic models, including those developed in the laboratory of Dr. Krzysztof Palczewski. These experiments used mice that have mutations in either the Rpe65 or Lrat genes, the same as those associated with LCA in humans. Both mouse models have clinical features of the human disease. The biological activity of the synthetic retinoid was monitored by measuring the level of pigment-related compounds in the eye. Retinal function was also assessed by detecting electroretinograms (ERGs) and electrical nerve signals from the retina. Oral administration of QLT091001 showed evidence of having corrected the biochemical defect in the retinoid cycle in light-sensing cells (rods) and appeared to restore ERG responses to light in both models of LCA. About QLT QLT Inc. is a biotechnology company dedicated to the development and commercialization of innovative therapies for the eye. We are focused on our commercial product Visudyne(R) for the treatment of wet-AMD, developing drugs to be delivered in our proprietary punctal plug delivery system, as well as developing our synthetic retinoid program for the treatment of certain inherited retinal diseases. For more information, visit our website at www.qltinc.com. In April of 2006, QLT entered into an exclusive worldwide co-development and licensing agreement with Retinagenix, LLC to develop active synthetic retinoid products for the treatment of degenerative retinal diseases. Under the terms of the agreement, QLT is responsible for developing and commercializing the products for use in ocular and all other human diseases. Retinagenix has participated in research in support of the co-development collaboration and is eligible to receive payments upon achievement of certain development, approval, and sales milestones as well as a royalty on net sales. Visudyne(R) is a registered trademark of Novartis AG. QLT Inc. is listed on The NASDAQ Stock Market under the trading symbol "QLTI" and on The Toronto Stock Exchange under the trading symbol "QLT."