ProQR’s Sepofarsen Improves Vision Significantly for Girl with LCA10
Eye On the Cure Research News
However, the Phase 2/3 Illuminate trial for sepofarsen didn’t meet its endpoints at 12 months
A 12-year-old girl virtually blind from Leber congenital amaurosis 10 (LCA10) and her family traveled 1,676 miles (2,698 kilometers) across Brazil for the chance to participate in the Phase 2/3 Illuminate clinical trial for sepofarsen, ProQR Therapeutic’s RNA therapy for the p.Cys998X mutation in the gene CEP290 causing her disease.
“Her parents were not expecting the therapy to work, and they understood their daughter might only get the placebo,” said Fernanda Belga Ottoni Porto, MD, PhD, the principal investigator for the trial at INRET Clínica/Santa Casa de Misericórdia de Belo Horizonte in Brazil. “But they wanted to participate in the trial to offer her eye for science as her eyes appeared to be otherwise useless. And the girl agreed with her parents.”
The young patient entered the trial, only able to see the motion of her hand in a very brightly lit room. That was the minimum vision required to participate in the trial.
Just a day after receiving an intravitreal injection of sepofarsen in one eye, her vision improved. “The vision in her treated eye, which had been her worse eye, surpassed the vision in what had been her best eye, the untreated eye,” recalled Dr. Porto. “I needed to teach her what the letter E looked like, so she could read the eye chart.”
As her vision improved further, the girl went from using Braille to learning to visually read the alphabet. She now watches television and can tell if a traffic light is green or red when she walks to school. She actively participates in the classroom and studies and works independently. And now, she can sign her name to paper.
Despite the dramatic vision improvements for the Brazilian girl, the overall Illuminate trial, after 12 months, didn’t meet its primary endpoint, improvement in best corrected visual acuity, nor its secondary endpoint, improvement in the ability to navigate a mobility course. The trial continues, and ProQR is in discussion with regulators to find a possible path forward to gain marketing approval.
Sepofarsen is an antisense oligonucleotide (AON), which works like "genetic tape" to mask the mistake in the patient’s messenger RNA, which convey genetic information for production of proteins that are critical for cells’ health and function.
AONs can be advantageous when large retinal disease genes — such as CEP290 or USH2A — exceed the capacity of viral gene delivery systems used in many emerging gene-augmentation therapies.