About LCA

What is Leber’s Congenital Amaurosis?
Leber’s congenital amaurosis (LCA) is the most common genetic cause of childhood blindness and affects about 15,000 patients in the Western world. For most patients there is currently no approved treatment available. The disease usually appears in the first year of life and is characterized by progressive loss of vision. In some cases, patients eventually become severely visually impaired and depending on the mutation, complete loss of vision will occur during early childhood.

In LCA, a process called phototransduction is disrupted in the light-detecting cells (rods and cones) in the retina, due to a mutation in a specific gene. Because these cells cannot perform their function properly, patients experience nystagmus (involuntary eye movement) and severely impaired visual function.

What causes Leber’s Congenital Amaurosis?
LCA is caused by mutations (or mistakes) in certain genes of the DNA. There are over 19 known gene mutations that can cause LCA. The most prevalent mutation is the p.Cys998X mutation, also known as c.2991+1655A>G mutation in the CEP290 gene. This mutation causes Leber's congenital amaurosis 10 (LCA10).
The CEP290 gene is responsible for expression of the CEP290 protein (centrosome- and cilium-associated gene centrosomal protein 290). LCA10 accounts for the most severe form of LCA. Although diagnosis rates vary, we believe approximately 2,000 patients in the Western world have LCA10 due to this mutation.

Amongst other functions, the CEP290 protein helps the development and maintenance of cilia in the photoreceptor cells (rods and cones) in the retina. A non-functioning CEP290 protein causes retinal degeneration in LCA 10 patients.
Treatment
There are currently no approved treatments for the underlying cause of LCA10.

About sepofarsen

ProQR is developing a novel drug, sepofarsen (QR-110), for patients with LCA10 due to the p.Cys998X mutation, also known as c.2991+1655A>G mutation, in the CEP290 gene.

QR-110 is designed to work in a unique way. It aims to repair the genetic defect in the RNA, enabling it to function as a normal “wild-type” mRNA. The RNA is the “blueprint” for protein synthesis and when repaired, it will produce a healthy CEP290 protein that is expected to have a normal function. The goal of sepofarsen is to repair the underlying defect in the RNA and potentially stop the progression of the disease or reverse some effects of LCA10 caused by the p.Cys998X mutation.

Sepofarsen has received orphan drug designation from the U.S. Food and Drug Administration and European Medicines Agency. Sepofarsen was also granted fast track designation by the U.S. Food and Drug Administration and access to PRIME program by the European Medicines Agency.

Clinical trials

PQ-110-001 - Phase 1/2 clinical study (ongoing, enrollment completed, top-line results available)
A Phase 1/2 clinical trial has been completed in children and adults with LCA10 due to the p.Cys998X mutation in the CEP290 gene.

Top-line results published in October 2019 suggest that the majority of patients treated with sepofarsen (QR-110) experienced a substantive overall improvement in vision at 12 months of treatment. The trial was conducted at three academic hospitals in the USA and Europe. Read more about the trial and the interim results on the clinical trial page.

Insight - open-label extension study (ongoing)


An open-label extension study, named “Insight”, is ongoing where eligible participants that complete the Phase 1/2 trial will be given the opportunity to continue treatment with sepofarsen.
Illuminate – pivotal Phase 2/3 clinical study (ongoing, enrollment in progress)


We are currently conducting “Illuminate”, a Phase 2/3 study in patients over eight years of age that have LCA10 due to the p.Cys998X mutation in the CEP290 gene. This trial began in April 2019.

Information for patients

Sepofarsen is an experimental medicine that we are developing for LCA10 patients with the p.Cys998X mutation in the CEP290 gene (also known as c.2991+1655A>G mutation). For the latest information about the program please visit our website where we will post regular updates. If you have any other questions, please read the FAQ below or contact us through the contact form and we will be happy to answer any question you have.

FAQ

Who is ProQR?
ProQR Therapeutics is a European company, founded in 2012 to develop a life-changing therapy for patients suffering from severe genetic disorders like Leber’s congenital amaurosis (LCA), Usher syndrome and autosomal dominant retinitis pigmentosa (adRP).
What is sepofarsen?
Sepofarsen (QR-110) is an experimental medicine that is designed to treat LCA10 patients with the p.Cys998X mutation in the CEP290 gene. Sepofarsen aims to restore a normal mRNA in patients resulting in normal CEP290 protein with the goal of stopping the progression or reversing the effects of the disease.
Can I participate in a sepofarsen clinical trial?
Patient enrollment is ongoing for “Illuminate”, a Phase 2/3 clinical study in patients over six years of age that have LCA10 due to the p.Cys998X mutation in the CEP290 gene. This trial is carried out in a number of expert centres in North America and Europe.

If you are interested in taking part in a sepofarsen clinical study, we suggest that you talk with your or your child’s treating physician to discuss your options. Additionally, you can find information about enrollment on www.clinicaltrials.gov.

Please visit this website if you would like to stay informed on our progress and future study participation opportunities.
I have a LCA CEP290 mutation other than p.Cys998X, is sepofarsen developed for me?
Sepofarsen is specifically designed to target the p.Cys998X mutation and is not expected to work in other mutations.
How often will sepofarsen be given?
We expect that sepofarsen will be a chronic treatment, meaning that patients will need to receive it on a regular basis. More information on the dosage and frequency of treatment will be gathered in clinical trials.
Will sepofarsen be available outside a clinical trial?
We have completed the first trial in people with Leber’s congenital amaurosis 10 (LCA10) with the p.Cys998X mutation in the CEP290 gene. ProQR has begun a Phase 2/3 study called "Illuminate".

While results of the first trial are encouraging, there is still much to learn about sepofarsen and its effects and therefore sepofarsen is currently not available outside a clinical study. ProQR will continue to assess this position as the program moves forward.

Please visit this website for the latest news and future study participation opportunities.

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