VANCOUVER, Canada I July 14, 2014 I QLT Inc. (Nasdaq:QLTI) (TSX:QLT) (“QLT” or the “Company”) today announced the publication of data from its Phase 1b proof-of-concept trial of QLT091001 in subjects with Leber Congenital Amaurosis (LCA) due to inherited genetic mutations in retinal pigment epithelium (RPE65) or lecithin:retinol acyltransferase (LRAT) in The Lancet. The peer-reviewed journal article is available first in the online edition of The Lancet at www.thelancet.com. In the study, treatment for 7 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 7 days of oral QLT091001 (12 subjects received 40 mg/m2 per day and 2 subjects received 10 mg/m2 per day). Patients were assessed at baseline and days 7, 9, 14, and 30, and every 2 months thereafter, for up to 3 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.
“Publication of this data in a preeminent journal such as The Lancet further highlights the importance of our findings and the potential of QLT091001 to rapidly improve visual function in patients with LCA,” stated Jason M. Aryeh, Chairman of the Board. “Together with our Phase 1b retreatment data reported earlier this year, these results underscore QLT091001’s value as a potential treatment for inherited retinal diseases due to RPE65 and LRAT mutations.”
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. 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 newborns worldwide, of which approximately 10% carry the inherited deficiencies of either RPE65 or LRAT.
About Retinitis Pigmentosa (RP) Due to RPE65 and LRAT Mutations
RP is a set of hereditary retinal diseases demonstrating clinical features similar to LCA. RP is also characterized by degeneration of rod and cone photoreceptors, but it presents with a more variable loss of vision in late childhood to adulthood. Deficits in dark adaptation and peripheral vision are particular hallmarks of RP. RP is currently estimated to affect at least 300,000 individuals worldwide, of which approximately 20%–30% are autosomal recessive (arRP). It is currently estimated that less than 3% of autosomal recessive RP patients carry the inherited deficiencies of either RPE65 or LRAT.
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, and is under investigation for the treatment of LCA and RP. QLT091001 has received orphan drug designations for the treatment of LCA (due to inherited mutations in LRAT or RPE65 genes) and RP (all mutations) by the FDA, and for the treatment of LCA and RP (all mutations) by the EMA. The drug has also been granted two Fast Track designations by the FDA for the treatment of LCA and RP due to inherited mutations in the LRAT and RPE65 genes. The FDA has also formally acknowledged that the orphan drug designations granted by the FDA on QLT091001 also cover QLT091001 for the treatment of Inherited Retinal Disease caused by LRAT or RPE65 mutations, including severe early childhood onset retinal dystrophy, which disease/condition we believe subsumes both LCA and RP. The clinical characteristics and progression of disease in LCA and RP overlap as do some of their genetic causes. At least 7 of the known LCA disease genes, including LRAT and RPE65, have also been linked to the clinical appearance of RP. Despite disease heterogeneity and terminology, there is an overlap in the genetic mechanisms underlying some forms of LCA and RP such as those caused by LRAT and RPE65 mutations where 11-cis-retinal production is either severely or completely compromised. RP is the most common inherited retinal disease, and is generally the diagnosis given to patients who begin to lose vision after the first decade of life, whereas the diagnosis of LCA is given to patients who have central vision loss soon after birth. There is no universally accepted diagnostic term for patients with characteristics in between; clinicians have considered such cases as either LCA or severe RP.
About QLT
QLT is a biotechnology company dedicated to the development and commercialization of innovative ocular products that address the unmet medical needs of patients and clinicians worldwide. We are focused on developing our synthetic retinoid program for the treatment of certain inherited retinal diseases.
QLT’s head office is based in Vancouver, Canada and the Company is publicly traded on NASDAQ Stock Market (symbol: QLTI) and the Toronto Stock Exchange (symbol: QLT). For more information about the Company’s products and developments, please visit our web site at www.qltinc.com.
On June 25, 2014, QLT entered into an Agreement and Plan of Merger (the “Merger Agreement”) among QLT, Auxilium Pharmaceuticals, Inc., a Delaware corporation (“Auxilium”), QLT Holding Corp., a Delaware corporation and a wholly owned subsidiary of QLT (“HoldCo”), and QLT Acquisition Corp., a Delaware corporation and a wholly owned subsidiary of HoldCo (“AcquireCo”). The Merger Agreement provides for a business combination whereby AcquireCo will be merged with and into Auxilium (the “Merger”). As a result of the Merger, the separate corporate existence of AcquireCo will cease and Auxilium will continue as the surviving corporation. On the date of the closing of the Merger, Auxilium will become an indirect wholly owned subsidiary of QLT (the “Combined Company”).
SOURCE: QLT
Post Views: 146
VANCOUVER, Canada I July 14, 2014 I QLT Inc. (Nasdaq:QLTI) (TSX:QLT) (“QLT” or the “Company”) today announced the publication of data from its Phase 1b proof-of-concept trial of QLT091001 in subjects with Leber Congenital Amaurosis (LCA) due to inherited genetic mutations in retinal pigment epithelium (RPE65) or lecithin:retinol acyltransferase (LRAT) in The Lancet. The peer-reviewed journal article is available first in the online edition of The Lancet at www.thelancet.com. In the study, treatment for 7 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 7 days of oral QLT091001 (12 subjects received 40 mg/m2 per day and 2 subjects received 10 mg/m2 per day). Patients were assessed at baseline and days 7, 9, 14, and 30, and every 2 months thereafter, for up to 3 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.
“Publication of this data in a preeminent journal such as The Lancet further highlights the importance of our findings and the potential of QLT091001 to rapidly improve visual function in patients with LCA,” stated Jason M. Aryeh, Chairman of the Board. “Together with our Phase 1b retreatment data reported earlier this year, these results underscore QLT091001’s value as a potential treatment for inherited retinal diseases due to RPE65 and LRAT mutations.”
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. 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 newborns worldwide, of which approximately 10% carry the inherited deficiencies of either RPE65 or LRAT.
About Retinitis Pigmentosa (RP) Due to RPE65 and LRAT Mutations
RP is a set of hereditary retinal diseases demonstrating clinical features similar to LCA. RP is also characterized by degeneration of rod and cone photoreceptors, but it presents with a more variable loss of vision in late childhood to adulthood. Deficits in dark adaptation and peripheral vision are particular hallmarks of RP. RP is currently estimated to affect at least 300,000 individuals worldwide, of which approximately 20%–30% are autosomal recessive (arRP). It is currently estimated that less than 3% of autosomal recessive RP patients carry the inherited deficiencies of either RPE65 or LRAT.
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, and is under investigation for the treatment of LCA and RP. QLT091001 has received orphan drug designations for the treatment of LCA (due to inherited mutations in LRAT or RPE65 genes) and RP (all mutations) by the FDA, and for the treatment of LCA and RP (all mutations) by the EMA. The drug has also been granted two Fast Track designations by the FDA for the treatment of LCA and RP due to inherited mutations in the LRAT and RPE65 genes. The FDA has also formally acknowledged that the orphan drug designations granted by the FDA on QLT091001 also cover QLT091001 for the treatment of Inherited Retinal Disease caused by LRAT or RPE65 mutations, including severe early childhood onset retinal dystrophy, which disease/condition we believe subsumes both LCA and RP. The clinical characteristics and progression of disease in LCA and RP overlap as do some of their genetic causes. At least 7 of the known LCA disease genes, including LRAT and RPE65, have also been linked to the clinical appearance of RP. Despite disease heterogeneity and terminology, there is an overlap in the genetic mechanisms underlying some forms of LCA and RP such as those caused by LRAT and RPE65 mutations where 11-cis-retinal production is either severely or completely compromised. RP is the most common inherited retinal disease, and is generally the diagnosis given to patients who begin to lose vision after the first decade of life, whereas the diagnosis of LCA is given to patients who have central vision loss soon after birth. There is no universally accepted diagnostic term for patients with characteristics in between; clinicians have considered such cases as either LCA or severe RP.
About QLT
QLT is a biotechnology company dedicated to the development and commercialization of innovative ocular products that address the unmet medical needs of patients and clinicians worldwide. We are focused on developing our synthetic retinoid program for the treatment of certain inherited retinal diseases.
QLT’s head office is based in Vancouver, Canada and the Company is publicly traded on NASDAQ Stock Market (symbol: QLTI) and the Toronto Stock Exchange (symbol: QLT). For more information about the Company’s products and developments, please visit our web site at www.qltinc.com.
On June 25, 2014, QLT entered into an Agreement and Plan of Merger (the “Merger Agreement”) among QLT, Auxilium Pharmaceuticals, Inc., a Delaware corporation (“Auxilium”), QLT Holding Corp., a Delaware corporation and a wholly owned subsidiary of QLT (“HoldCo”), and QLT Acquisition Corp., a Delaware corporation and a wholly owned subsidiary of HoldCo (“AcquireCo”). The Merger Agreement provides for a business combination whereby AcquireCo will be merged with and into Auxilium (the “Merger”). As a result of the Merger, the separate corporate existence of AcquireCo will cease and Auxilium will continue as the surviving corporation. On the date of the closing of the Merger, Auxilium will become an indirect wholly owned subsidiary of QLT (the “Combined Company”).
SOURCE: QLT
Post Views: 146
