LCA10 CEP290 Illuminate Clinical Trial Produces No Observed Benefit

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ProQR Therapeutics’ clinical trials of sepofarsen to treat a form of Leber congenital amaurosis (LCA) caused by a mutation in the CEP290 gene did not meet its primary endpoint of improving visual acuity.

Illuminate, the name of the clinical study, aimed to explore whether the investigational medicine sepofarsen was effective and safe for people with LCA10 caused by the CEP290 mutation.

The Phase 2/3 clinical trial produced no observed benefit in visual acuity for participants receiving the treatment versus those in the study not receiving the treatment. Visual acuity is a measure of the ability of the eye to distinguish shapes and details of objects at a given distance.

ProQR Founder and Chief Executive Officer Daniel A. de Boer delivered the news recently and characterized the results as disappointing.

“Given the results observed in earlier studies of sepofarsen, the Illuminate trial results are unexpected and disappointing, especially for people living with LCA10,” de Boer said.

“ProQR was founded with the goal of developing RNA therapies  (ribonucleic acid)  for patients with high unmet medical need, and we will continue to advance our robust pipeline of therapies for genetic eye disease. We are deeply grateful to all of the participants, their supporters, and investigators who participated in the Illuminate study.

“Since the results in February, ProQR has been conducting additional analyses of Illuminate and will present these findings at a future scientific conference.”

ProQR works on developing RNA therapies to treat LCA and other inherited rare diseases (IRDs). With DNA being the library of our genes and RNA being a blueprint of that collection, RNA therapies help carry out DNA instructions to create certain proteins critical to a healthy cell.

Analyzing Results for More Answers

Hope in Focus Co-Founder and Board Chair Laura Manfre said we will share updates with the LCA community as we learn more from ProQR.

“The results are not what we had hoped for from ProQR on the LCA10 Phase 2/3 trial, but we are resolved to keep hope in focus, knowing that the brilliant minds that got us this far are not giving up.

“It’s important to remember when there are setbacks that only 10 years ago, all we had was hope. Most of the community couldn’t even get a genetic diagnosis, let alone hope for treatment,” she said. “We’ve come a long way in a short period of time, and we’re going to keep advancing.”

Ben Yerxa, PhD, Chief Executive Officer of the Foundation Fighting Blindness, said his organization will work with ProQR to learn more about the data.

“This was not the outcome we had hoped for, and we share in the disappointment many are feeling in the community,” Yerxa said.

“We will continue to work alongside ProQR to learn more from the ongoing analyses and as they work to advance RNA therapies to potentially help children, adults, and families who are affected by rare genetic eye diseases.”

In delivering the results, the biotechnology company gave background about LCA, the most common genetic cause of childhood blindness, affecting about 15,000 people in the Western world. One federally approved gene therapy treatment, LUXTURNA®, exists for people with LCA2 (RPE65), one of the more than 27 forms of LCA.

The rare retinal disease usually appears in the first year of life and is characterized by progressive loss of vision. Other symptoms can include rapid eye movement, known as nystagmus, eye-poking, night blindness, and sensitivity to light, known as photophobia. Depending on the mutation, complete loss of vision can occur during early childhood.


Specifics of the LCA10 CEP290 Trial

Illuminate enrolled 36 participants, aged 8 years or older with genetically confirmed LCA10 due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290 gene.

The study was a randomized, sham-controlled clinical trial that took place in three randomized groups at 14 sites in nine countries.

The first group received a target dose of sepofarsen by intravitreal injection (IVT), the second received a low dose via IVT, and the third underwent a sham procedure that mimicked an injection with no medicine or injection given.

Bart P. Leroy, MD, PhD, one of the study’s key investigators and Director of the Ophthalmic Genetics and Retinal Degenerations clinics in the Division of Ophthalmology and Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia (CHOP), said work will continue toward finding therapies.

“LCA10 is devastating, and with no approved therapies, very difficult to treat retinal disease resulting in blindness,” said Dr. Leroy, who also is head of the Ophthalmology Department at Ghent University Hospital and Professor of Ophthalmology and Ophthalmic Genetics at Ghent University in Belgium.

“We will continue to work with ProQR to understand the data as they work for advance therapies for individuals with inherited retinal diseases.”

Andy Bolan, ProQR Director of Medical Affairs, said the team extends its thanks to the study participants, their supporters, the investigators, and their staff for support in developing the trial. He said the biotech remains committed to making a significant and positive impact on the lives of those affected by genetic conditions.

For quarterly news and future study participation opportunities, you can sign up for the ProQR Eye Connect Newsletter or follow them on social media.

People also can contact ProQR with any questions at








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