ProQR Therapeutics has encouraging early data from a small study that show its experimental RNA-based therapy for a rare, inherited form of vision loss helped patients recover some of their sight. Based on those results, the company is planning to advance its therapy to two pivotal studies that could start later this year.
Netherlands-based ProQR is developing its experimental therapy, QR-421a, as a treatment for Usher syndrome. The rare disorder is caused by mutations to genes that provide the instructions for proteins key to hearing, vision, and balance. The disorder is classified under three types, according to genetic origin. There are no FDA-approved drugs to treat any of the Usher types.
The ProQR treatment addresses type 2, which is caused by mutations to the USH2A gene. The RNA therapy, which is injected into the eye, is designed to get a cell’s protein-making machinery to skip exon 13. That’s the mutated segment of the string of genetic material used to make usherin, a protein key for vision. By skipping the mutated exon, the ProQR drug is intended to restore a cell’s ability to produce functional versions of usherin. The hope is that these versions of the protein will stop vision loss or even restore some of it.
ProQR tested its RNA therapy in a dose-ascending Phase 1/2 study enrolling 20 patients. In the clinical trial, patients served as their own controls—the treated eye was compared to the untreated eye. But the study also included a small group of six patients who were given a sham treatment. The study followed patients for up to 48 weeks.
The main goal of the clinical trial was to assess safety and tolerability, and the RNA therapy met those marks with no adverse events reported, according to an investor presentation. The therapy also achieved secondary goals of showing improvement according to several measures of vision, including retinal imaging.
The data announced Wednesday were collected from a planned interim analysis. With the encouraging preliminary data, ProQR now wants to see if its therapy can produce the same results in a larger group of patients followed for a longer period. The company is planning two Phase 2/3 studies, one in patients with advanced Usher and the other in patients in early to moderate stages of the disease, according to the investor presentation. The 24-month clinical studies will enroll 100 patients and the main goal will be to measure visual acuity. If ProQR gets regulatory clearance for its clinical trial plan, the company expects to begin the studies by the end of this year.
A Phase 2/3 study in Usher syndrome would give ProQR a second program in pivotal testing. The company is currently testing another RNA therapy, sepofarsen, in a Phase 2/3 clinical trial in a different rare inherited retinal disease, Leber congenital amaurosis type 10. The study is evaluating the therapy in patients who have a particular genetic mutation. That clinical trial has completed enrollment and is expected to produce preliminary data in the first half of next year, according to the company’s annual report.
Photo by Flickr user Ken Teagardin via a Creative Commons license
