First Pediatric Patient with Rare Genetic Eye Disease Dosed in Clinical Trial

ProQR Therapeutics has announced the first pediatric clinical trial participant has been treated in its new clinical trial named Brighten of the experimental RNA therapy sepofarsen.

Brighten is a clinical study for children under 8 years old with Leber congenital amaurosis (LCA) due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290 gene. Around 15 children will participate in the clinical trial.

The pediatric participants will receive sepofarsen through intravitreal injections at one of five different dose levels. The aim of the Brighten study is to find out whether injections with sepofarsen are safe and tolerated in children with LCA.

Participants receive the study medicine up to a maximum of four times in one eye, the other eye remains untreated as a control. The treatment will be given on day one, followed by a dose every six months in the study. The clinical trial is being conducted at several hospitals in Europe.

Sepofarsen is an investigational RNA therapy that aims to restore vision loss in people with Leber congenital amaurosis due to a specific mutation in the CEP290 gene. This c.2991+1655A>G mutation, also known as p.Cys998X, causes a mistake in the CEP290 RNA and therefore a process called splicing is not done properly. The cell can therefore not use the RNA to produce a working CEP290 protein that is essential for vision.

Sepofarsen works by binding to the mutated CEP290 RNA to enable correct splicing. The cells in the retina can then produce the CEP290 protein again.

Sepofarsen has shown encouraging results in an early phase 1/2 clinical trial and is now tested in a late-stage Phase 2/3 clinical trial named Illuminate.

Leber congenital amaurosis (LCA) is the most common cause of blindness due to genetic disease in children. It consists of a group of diseases of which LCA10 is the most frequent and one of the most severe forms. LCA10 is caused by mutations in the CEP290 gene, of which the c.2991+1655A>G (p.Cys998X) mutation is the most common.

LCA10 leads to early loss of vision causing most people to lose their sight in the first few years of life. To date, there are no treatments approved that treat the underlying cause of the disease. Approximately 2,000 people in the Western world have LCA10 because of this mutation.