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Dutch company ProQR announces the receipt of FDA authorisation to initiate Phase I/II study for Leber congenital amaurosis, type 10 (LCA10)

Dutch biotechnology company ProQR Therapeutcis N.V., (NASDAQ:PRQR), Leiden, The Netherlands, has announced the receipt of “fast-track” designation from the FDA for their clinical stage development of “QR-110”, an experimental gene editing treatment for Leber’s congenital amaurosis (LCA), type 10. Fast track designation is granted by the FDA to sponsors of treaments under development for serious conditions with an unmet medical need and is designed to expedite the development process through more frequent FDA interactions and review. The treatment has already been granted orphan drug designation in the United States and the European Union.


LCA10 is the most common form of LCA in Europe and North America, arising from mutations in the CEP290 gene. While most CEP290 patients have profound vision loss, fundus examination and OCT analysis show a relatively well-preserved central macular anatomy well into the third decade of life. Despite such, LCA10 is one of the most severe forms of juvenile retinopathies and the most common mutation found in such LCA patients is the p.Cys998X error in CEP290, a nonsense mutation understood to account for up to 20% of all LCA patients in north western Europe. While there are no approved treatments yet available for the disease, several academic and commercial teams are actively engaged in a number of gene therapy related development programmes.


According to ProQR Therapeutics, QR-110 is a “first-in-class” investigational RNA-based oligonucleotide, designed to target the underlying cause of LCA Type 10 – the p.Cys998X mutation in the CEP290 gene. This mutation results in a substitution of one nucleotide in the pre-mRNA that subsequently causes aberrant splicing of the mRNA transcript yielding a non-functional CEP290 protein. The ProQR therapy is designed to bind the mutated sequence in the pre-mRNA CEP290 transcript to reconstitute normal splicing of the pre-mRNA and production of the wild-type protein, so called RNA-editing. The drug is currently being formulated for intravitreal administration which should provide a realtively straight-forward out-opatient procedure, subject to regulatory approval. The company intends to conduct an open-label clinical trial with approximately 6 children (aged between 6-17 years) and 6 adults (≥ 18 years) with a confirmed diagnosis of LCA 10 arising from one or two copies of the p.Cys998X mutation. Patients are scheduled to receive up to four intravitreal injections of QR-110 into one eye every three months for one year, with preliminary results expected in 2018.


Commenting on the development, Noreen R. Henig, Chief Medical Officer of ProQR stated that, “QR-110 is a unique and elegant approach to addressing the underlying genetic defect that leads to blindness in individuals with LCA 10 due to the p.Cys998X mutation. We are very pleased with granting of the Fast Track designation by the FDA for this program as it highlights the need for innovative and efficacious medicines for this devastating disease for which there is currently nothing available. We are also excited to be able to initiate our first trial for QR-110 as a multidose study and for that we will benefit from the Fast Track Designation. We believe development of QR-110 also opens the possibilities for RNA approaches to target other causes of genetic blindness. We are building our pipeline in ophthalmology and will use our rapid development approach to QR-110 as a model for how to bring RNA therapeutics to patients in need.”