A Dutch biotechnology company, ProQR Therapeutcis N.V., (NASDAQ:PRQR), Leiden, has announced the enrolment of a phase 2/3 study for the treatment of Leber Congenital Amaurosis 10 (LCA10), due to the p.Cys998X mutation in the CEP290 gene. The randomized study will comprise 36 patients, aged eight years or older, that will receive either sepofarsen at the target registration dose, a low dose, or sham treatment. The study is registered at ClinicalTrials.gov (NCT03913143) and its primary endpoint is the mean change from baseline in BCVA at month 12. According to the company, top-line results from the study are expected in the first half (H1) of 2022.
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. 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 relatively straight-forward procedure, subject to regulatory approval. Commenting on the announcement of the phase 2/3 trial, Aniz Girach, MD, Chief Medical Officer of ProQR, stated that, “we are pleased to have completed enrolment of the pivotal Illuminate trial of sepofarsen. This marks an important milestone for ProQR, as well as for the LCA10 and broader inherited retinal disease community. In surpassing our enrollment target, we were able to accommodate the broad interest to participate in the trial. This speaks to the fact that there are currently no approved treatments for patients with LCA10”.