Feb 15, 2022

ProQR’s Phase 2/3 Clinical Trial for LCA10 RNA Therapy Doesn’t Meet Endpoints

Eye On the Cure Research News

The emerging treatment had shown encouraging results in a Phase ½ clinical trial

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ProQR, an RNA therapy development company in the Netherlands, has reported that its Phase 2/3 ILLUMINATE clinical trial of sepofarsen did not meet its primary endpoint of best corrected visual acuity (BCVA), nor did it meet secondary endpoints, which included mobility. The emerging RNA therapy was designed for people with Leber congenital amaurosis 10 (LCA10) caused by the mutation p.Cys998X in the gene CEP290. The company will further analyze results from the study.

Launched in April 2019, the ILLUMINATE trial has been taking place at 14 sites in nine countries. Participants were randomly assigned to one of three groups: patients receiving 40 mcg of sepofarsen, patients receiving 80 mcgs of sepofarsen, or those receiving a sham procedure (placebo). The treatment was delivered by an injection into the vitreous, the soft gel in the middle of the eye.

The ILLUMINATE trial was launched after 60 percent of patients in the Phase 1/2 trial had improvements in visual acuity and their ability to navigate a mobility course.

“We are, of course, disappointed in the news for sepofarsen. It is an important reminder that in clinical trials for emerging treatments, unfortunately, we don’t always meet our goals. It is part of the process for all biomedical research,” says Claire Gelfman, PhD, chief scientific officer at the Foundation Fighting Blindness. “But there is a lot we are learning from ILLUMINATE that can be applied to future development of RNA therapies and human studies.

Sepofarsen is an antisense oligonucleotide (AON), which, in this example, works like "genetic tape" to block 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 convey 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.

The Foundation Fighting Blindness is investing $7.5 million through its RD Fund for ProQR’s development of an AON for people with Usher syndrome or retinitis pigmentosa caused by mutations in exon 13 in the USH2A gene, which recently moved into two Phase 2/3 clinical trials.

The RD Fund, a venture philanthropy fund, was established in 2018 to provide investments for promising retinal degenerative disease therapies that are in, or moving toward, early human studies. The RD Fund currently has $114 million in assets and investments in 12 projects.