ProQR Therapeutics' lead RNA therapy failed to meet primary and secondary endpoints in a pivotal study that tested it for the treatment of a rare inherited vision disorder. Despite disappointing preliminary data, the biotech company said it remains confident in the technology that spawned the investigational therapy, sepofarsen, and that the Phase 2/3 trial is proceeding.

An RNA therapy from ProQR Therapeutics has failed a key test in an inherited eye disorder, an unexpected setback for the most advanced program in biotechnology. According to preliminary results, patients who received the experimental treatment sepofarsen showed no difference compared to the control group.

The phase 2/3 study in patients with congenital hepatic amaurosis also failed to meet the secondary objectives of evaluating other visual parameters. Based in Leiden, the Netherlands, ProQR said it will continue to analyze the data and present more details at a future medical meeting. In a conference call Friday, CEO Daniel de Boer expressed surprise and disappointment at the initial data from the study, dubbed ILLUMINATE.

"We're going to find out what happened to Sepofarsen's ILLUMINATE trial, where we're leaving no stone unturned," de Boer said.

Leber congenital amaurosis (LCA) is a disease in which the photoreceptors in the retina degenerate or stop working properly. The disease is due to genetic mutations; Defects in the CEP290 gene result in the most common and severe form, called LCA10. Those born with LCA10 usually lose their vision in the first years of life. There are no treatments for the underlying cause of the disease.

ProQR aims to treat LCA10 by correcting the genetic defect that causes it. Sepofarsen is an RNA therapy designed to restore the ability of the CEP290 gene to produce functional CEP290 protein. The treatment stems from a ProQR platform technology that has spawned five programs, all of them inherited retinal diseases, that the biotech plans to treat with RNA therapies delivered as injections into the eye.

The pivotal phase 2/3 trial of sepofarsen enrolled 36 patients 8 years of age and older who had genetically confirmed LCA10 due to a CEP290 mutation. These patients were randomly assigned to three groups: a low or high dose of sepofarsen, or a third group that underwent a sham procedure that mimics an injection.

The main objective of the study was to measure the best corrective visual acuity according to a widely used visual assessment, in which a negative value indicates an improvement in vision and a positive value indicates a deterioration in vision. According to ProQR, the mean change from baseline in best visual acuity at 12 months was -0.11 in the high-dose group and -0.13 in the low-dose group. In the group of patients who received a sham procedure, the mean change in score was -0.12.

Secondary study endpoints included a full-field stimulus test, which is a measure of the lowest flash of light eliciting visual stimulation, and mobility class performance. For these measures, ProQR also reported no difference between the treatment groups and the sham arm.

No serious adverse events were reported in the study, and RNA therapy was well tolerated by patients. Medical director Aniz Girach said cataracts, cystoid macular edema and thinning of the retina were observed; these findings are consistent with what was reported in the phase 1/2 trials of sepofarsen. In this study, involving five children and six adults, ProQR reported "rapid and sustained improvement in vision" in the majority of patients, paving the way for the pivotal phase 2/3 study. The 12-month data reported Friday are the first results from this three-year study, which is ongoing, de Boer said. In response to an analyst's question about whether another study of sepofarsen was needed, de Boer said ProQR won't know until the company has a better understanding of the results of the current study.

"Everything is on the table," de Boer said. "We can contact you once we've done that analysis."