ProQR Therapeutics has announced positive interim results from its phase 1/2 clinical trial evaluating QR-110
as a potential treatment for Leber’s congenital amaurosis 10 (LCA10). The therapy demonstrated rapid and sustained improvement in vision in the majority of participants and was found to have a favorable safety profile.
“The results of this interim analysis are encouraging and met our decision criteria to stop enrollment in this study and progress to a pivotal phase 2/3 trial,” said David Rodman, MD, executive vice president of research and development of ProQR, in a recent statement.
“We observed a clinically meaningful improvement in vision in the treated eye as measured by both mechanistic and potential registration endpoints. Consistent with predictions based on our patient derived optic-cup models, improvement in visual function was observed as early as 2 months after treatment and was maximal and stable by 3 months and thereafter.”
After just 3 months of treatment, 60% of participants showed a clinically meaningful response in visual acuity and mobility course endpoints; there was general concordance across the endpoints, according to a recent news release. Within 2 months, efficacy signals were noted with maximal benefits observed within 2 to 3 months post-treatment initiation. Upon assessing all available data in a secondary analysis, recorded effects on efficacy were found to be durable beyond 3 months.
A substantive overall improvement in best corrected visual acuity (BCVA) was also observed in the majority of participants. Improvement measures and judgements were based off of the Berkeley Rudimentary Vision Test (BRVT) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. Additionally, the mean improvement at 3 months (and standard error of mean, SEM) was -0.67 LogMAR (SEM 0.32) with 62.5% of individuals displaying a clinically meaningful improvement consisting of an improvement greater than -0.3 LogMAR from baseline. In the contralateral eye, the mean change was 0.02 LogMAR (SEM 0.05).
Correlations between effects on visual acuity and effects on mobility were also observed, with a substantive overall improvement in functional visual performance occurring in the majority of patients. A series of mobility courses at increasing difficulty and multiple light intensities were used to make the assessments. The mean improvement in navigating the mobility course was 2.6 levels (SEM 1.2) with 57.1% of participants improving by more than 2.0 levels, an improvement that is considered clinically meaningful. In the contralateral eye, the mean change was 1.36 (SEM 1.04).
A meaningful increase in participants’ ability to detect flashes of red or blue light as determined by the FST showed improvements in visual function. In red light sensitivity, treatment mean improvement was -0.74 log Cd/m2
(SEM 0.35) at 3 months. In blue light sensitivity, treatment mean improvement was -0.91 log Cd/m2
(SEM 0.38) at 3 months. Furthermore, with a mean change of log -0.14 mm (SEM 0.08) in OCI, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients).
To date, no serious adverse events related to QR-110 treatment has occurred, and QR-110 has been found to be well tolerated. “Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days,” according to the news release.
“We are very encouraged by the positive results of the phase 1/2 trial in LCA10,” Dr. Rodman told Rare Disease Report®
. This is a devastating disease with no current therapy, so progress is exciting not only to us, but more importantly to the patients and their families. These data validate our RNA oligo-based platform for discovering treatments for rare genetic eye diseases. We are looking forward to designing and implementing a pivotal phase 2/3 trial for QR-110 in LCA10 that could serve as the sole registration trial for the program. We expect to start this trial during the first half of 2019.”
The pivotal phase 2/3 trial, ILLUMINATE, has a preliminary double-blind, controlled, 12-month design. Thirty to 40 patients with LCA10 due to 1 or 2 copies of the p.Cys998X mutation that could be adaptively repowered are anticipated to enroll in the trial. The mobility course and visual acuity are expected to serve as the trial’s primary endpoints, among others.
ProQR also plans to start a trial that will enroll patients younger than 6 years of age with LCA10 in parallel to the pivotal phase 2/3 trial.