ProQR’s RNA Therapy for USH2A Performs Well in Phase 1/2 Clinical Trial

ProQR, a developer of RNA therapies in the Netherlands, has reported improvements in vision and retinal structure for patients in its Phase 1/2 Stellar clinical trial for QR-421a, an RNA therapy for people with mutations in exon 13 of the USH2A gene. These mutations cause Usher syndrome type 2A (USH2A) or non-syndromic retinitis pigmentosa (RP). According to ProQR, more than 16,000 in the Western world have USH2A or RP caused by these mutations.

As a result of these findings, ProQR is planning two Phase 2/3 trials for QR-421a. Both trials are expected to start by the end of 2021. The Sirius trial will enroll approximately 100 patients with advanced vision loss. The Celeste trial will enroll approximately 100 patients with early-moderate vision loss.

“We are very pleased to see these results for QR-421a in ProQR’s Phase 1/2 trial and the company’s plans for Phase 2/3 studies by the end of the year,” says Benjamin Yerxa, PhD, chief executive officer, Foundation Fighting Blindness. “With its LCA-CEP290 treatment in a Phase 2/3 trial, ProQR is demonstrating well that its RNA therapies have encouraging potential for people with inherited retinal diseases.”

The Foundation Fighting Blindness invested $7.5 million through its RD Fund to move QR-421a into and through the early stage clinical trial. 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.

QR-421a is an antisense oligonucleotide (AON) — a small piece of genetic material — designed to mask exon 13 mutations in the RNA of USH2A. RNA are genetic messages that cells read to make proteins critical to their health and function. QR-421a enables retinal cells to skip over exon 13 (and any mutations inside it) when reading the USH2A RNA, enabling the cells to make functional protein that will hopefully halt or slow the disease process and vision loss.

In the Phase 1/2 Stellar trial, QR-421a demonstrated benefits in best corrected visual activity (BCVA); static perimetry, which measures light sensitivity in the peripheral retina; and retinal structure as measured by optical coherence tomography (OCT). Improvements in BCVA were greatest for the six treated patients with advanced disease. Improvements in perimetry were greatest for the eight treated patients with early-moderate disease. All 14 treated patients received one dose of QR-421a, and results were reported at 48 weeks after treatment. Based on observations of durability, retreatment at 24 weeks is believed to be optimal.