ProQR, a biotech company in the Netherlands, has reported vision improvements for patients in a Phase 1/2 clinical trial for QR-110, a therapy for people with Leber congenital amaurosis 10 (LCA10), which is caused by the p.Cys998X mutation in the CEP290 gene. The mutation is estimated to affect about 2,000 people in the Western world.
The company reported that 60 percent of subjects in the trial demonstrated improvements in visual acuity and their ability to navigate a mobility course. The treatment was also safe for patients.
As a result of the encouraging interim results, ProQR has concluded the Phase 1/2 trial and plans to move the treatment into a Phase 2/3 clinical trial. Ten people were treated in the Phase 1/2 study.
Results from the interim analysis were presented on September 5, 2018, at the Retinal Degeneration 2018 meeting in Killarney, Ireland, by principal investigator Artur Cideciyan, PhD, research professor of ophthalmology at the Scheie Eye Institute, University of Pennsylvania.
The Foundation Fighting Blindness has entered into a partnership with ProQR to develop a retinal therapy for people with Usher syndrome type 2A (USH2A) caused by mutations in exon 13 of the USH2A gene. FFB will be investing up to $7.5 million in milestone-based funding to advance the treatment, known as QR-421a.
“The results from ProQR’s trial are great news for people with LCA10. Furthermore, the safety and vision improvements observed in the study provide strong evidence that antisense oligonucleotides, ProQR’s treatment approach, are an effective way to save and restore the vision of people with retinal diseases,” says Ben Yerxa, PhD, chief executive officer at FFB. “ProQR’s results for QR-110 are groundbreaking, because it is the first time this treatment approach has improved vision in humans with retinal disease.”
ProQR’s LCA10 therapy is an antisense oligonucleotide (AON), which works like “genetic tape” to repair the mutation. Unlike gene replacement therapies in which copies of whole genes are delivered to replace defective copies, AONs correct the mutation in the patient’s messenger RNA, which conveys genetic information for protein production. AONs can be advantageous when large retinal-disease genes — such as CEP290 or USH2A — exceed the capacity of viral gene-replacement delivery systems.
Patients in the LCA10 Phase 1/2 trial are receiving four intravitreal injections of QR-110 into one eye—one injection every three months. The trial is being conducted at three centers: the University of Iowa, Iowa City, Iowa; the Scheie Eye Institute at the University of Pennsylvania, Philadelphia; and the Ghent University Hospital, Ghent, Belgium.