ProQR Therapeutics announces QR-110 trial

Posted on: Tuesday, November 21st, 2017



ProQR Therapeutics N.V. has announced that the first patient has been dosed in the Phase I / II open-label trial assessing the safety, tolerability, pharmacokinetics and efficacy of QR-110. The trial will enrol approximately six adults and six children who have Leber’s congenital amaurosis ten (LCA 10) due to the p.Cys998X mutation in the CEP290 gene. Subjects will receive a dose of QR-110 every three months for a total of four doses in one eye. The trial is planned to be conducted at three specialised centres: the University of Iowa, Iowa City, IA, US, the Scheie Eye Institute at the University of Pennsylvania, Philadelphia, PA, US and the Ghent University Hospital, Ghent, Belgium.

Benjamin Yerxa, PhD., Chief Executive Officer at Foundation Fighting Blindness, stated, “We are delighted with the launch of ProQR’s clinical trial for its treatment for people with devastating vision loss caused by the p.Cys998X mutation in CEP290. There are no other options for these patients, and furthermore, we believe most emerging gene replacement technologies do not have the capacity to deliver the large CEP290 gene to the retina.”

QR-110 is ProQR’s lead program in the ophthalmology pipeline that also includes two programs for Usher syndrome, a program for Fuchs endothelial corneal dystrophy and a program for Stargardt’s disease. QR-110 is ProQR’s second program to enter clinical development, following QR-010, which is being developed for the most common mutation causing cystic fibrosis.

“This announcement recognizes an important next step towards achieving our goal of developing precision medicines based on molecular diagnostics and our RNA therapeutic platform,” said David M. Rodman, MD, Chief Development Strategy Officer of ProQR. “The QR-110 program is the first in a planned series of ophthalmology trials utilizing our RNA therapy platform to target the underlying cause of blindness in patients with inherited forms of retinal dystrophy. We expect this trial will give us fundamental information regarding the safety, efficacy and developability of QR-110 in adults and children with LCA 10.”

Key facts on QR-110

• QR-110 aims to delay the progression of the disease or restore vision in people with LCA 10 due to the p.Cys998X mutation in the CEP290 gene.
• QR-110 is a single stranded RNA oligonucleotide designed to restore wild-type or normal CEP290 mRNA.

• In pre-clinical studies of QR-110, it was shown to convert close to 100% of the mutant mRNA to wild-type in a homozygous optic cup organoid model.
• A long half-life in the eye allowing for infrequent dosing.

• Administered through intravitreal administration, which is considered a routine procedure.

• A ProQR sponsored pre-evaluation / retrospective natural history study collecting data of 22 LCA 10 patients over a period of 16 years was completed in 2017 (Samuel G. Jacobson et al; Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the Intronic Mutation in the CEP290 Gene. Invest. Ophthalmol. Vis. Sci. 2017;58(5):2609-2622.)

About the PQ-110-001 trial
PQ-110-001 is an open-label trial that will include approximately six children (age 6 – 17 years) and six adults (≥ 18 years) who have LCA 10 due to one or two copies of the p.Cys998X mutation in the CEP290 gene. During the trial, subjects will receive four intravitreal injections of QR-110 into one eye; one every three months. The QR-110 trial is expected to be conducted in three centres with significant expertise in genetic retinal disease in the US and Europe.

The objectives of the trial will include safety, tolerability, pharmacokinetics and efficacy as measured by restoration or improvement of visual function and retinal structure through ophthalmic endpoints such as visual acuity, full field stimulus testing (FST), optical coherence tomography (OCT), pupillary light reflex (PLR), mobility course and fixation stability. Changes in quality of life in the trial subjects will also be evaluated. Interim safety and efficacy trial results from the majority of patients after 6 months of treatment are expected in 2018, full 12 month treatment data from all patients in the trial are expected in 2019.