ProQR Therapeutics N.V., a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for QR-421a. QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome type 2 and non-syndromic retinitis pigmentosa (RP) due to mutations in exon 13 of the USH2A gene.
ProQR announces clearance of IND to start clinical trial of QR-421a in Usher syndrome type 2 patientsWednesday, December 5, 2018
Usher syndrome is the leading cause of combined deafness and blindness. Exon 13 mutations in the USH2A gene targeted by QR-421a cause vision loss in approximately 16,000 individuals in the Western world. ProQR plans to start enrolling patients in a Phase 1/2 trial named STELLAR in the coming months with preliminary data expected in mid-2019.
“We are pleased to be advancing QR-421a, our second therapy for an inherited retinal disease, into the clinic and continuing the development of our portfolio of transformative RNA medicines for severe genetic rare diseases,” said Daniel A. de Boer, Chief Executive Officer of ProQR. “QR-421a has shown promising activity in both the optic cup and zebra fish models and we are excited about the potential to make a meaningful impact for Usher syndrome patients.”
QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of vision loss in Usher syndrome type 2 and non-syndromic retinitis pigmentosa (RP) due to mutations in exon 13 of the USH2A gene. Mutations in this exon can cause loss of functional usherin protein that causes the disease. QR-421a is designed to exclude the genetic defect from the RNA in the eye, such that it leads to the expression of a shortened but functional usherin protein, thereby modifying the underlying disease. QR-421a has received orphan drug designation in the United States and the European Union.
About the Phase 1/2 “STELLAR” trial
STELLAR, or PQ-421a-001, is a first-in-human study that will initially include approximately 18 adults who have vision loss due to mutations in exon 13 of the USH2A gene and will be conducted at expert sites in the US and Europe. It will be a double-masked, randomized study exploring several dose levels and a control (sham injection), given as a single intravitreal injection of QR-421a into one eye. The first patient at each dose level will be dosed in an open-label manner. The objectives of the trial will include evaluation of safety, tolerability, pharmacokinetics and efficacy, as measured by restoration or improvement of visual function and retinal structure through ophthalmic endpoints such as visual acuity (BCVA), visual field and optical coherence tomography (OCT). Changes in quality of life in the trial subjects will also be evaluated
Data from the first-in-human study are expected in mid-2019. Patients completing this trial will be able to participate in an extension study if eligible. Results from the single dose trial will inform the next stage that will potentially include a seamless adaptive, multi-dose, controlled trial.
About Usher Syndrome
Usher syndrome is the leading cause of combined deafness and blindness. Patients with this syndrome generally progress to a stage in which they have very limited central vision and moderate to severe deafness. Usher syndrome type 2 is one of the most common forms of Usher syndrome and is caused by mutations in the USH2A gene. To date, there are no approved treatments or products in clinical development that treat the vision loss associated with Usher syndrome type 2.
ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases such as Leber’s congenital amaurosis 10, dystrophic epidermolysis bullosa and cystic fibrosis. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.