Rare Daily Staff

ProQR Therapeutics said the U.S. Food and Drug Administration has cleared its Investigational New Drug application for QR-1123 to treat vision loss associated with autosomal dominant retinitis pigmentosa, a rare eye disease.

ProQR plans to start enrolling patients in a phase 1/2 trial for QR-1123 before the end of the year.

Autosomal dominant retinitis pigmentosa, or adRP, is a severe genetic condition that causes progressive reduction in night and peripheral vision during childhood and frequently leads to blindness in mid adulthood. In the United States, the most prevalent mutation associated with adRP is the P23H point mutation in the rhodopsin (RHO) gene and affects approximately 2,500 people. This gain of function mutation causes misfolding of the rhodopsin protein that becomes toxic to the photoreceptor cells in the retina. Over time the cells die and vision is progressively lost. There are currently no therapies approved or in clinical development for P23H adRP.

QR-1123 is a first-in-class investigational antisense oligonucleotide designed to address the underlying cause of the vision loss associated with adRP due to the P23H mutation in the RHO gene. It was discovered and developed by Ionis Pharmaceuticals using Ionis’ proprietary antisense technology and in-licensed by ProQR in 2018. The therapy aims to inhibit the formation of the mutated toxic version of the rhodopsin protein by specifically binding the mutated RHO mRNA. Binding of QR-1123 causes allele specific knockdown of the mutant mRNA by a mechanism called RNase H mediated cleavage without affecting the normal RHO mRNA. QR-1123 is intended to be administered through intravitreal injections in the eye.

“This represents our fifth IND in less than five years and our third clinical program for severe genetic eye diseases,” said Daniel de Boer, CEO of ProQR. “With a strong in vitro and in vivo proof-of-concept, we are excited about the potential of this medicine to make a positive impact on the lives of patients with adRP.”

The planned trial is a first-in-human study that will initially include up to 12 adults with adRP due to the P23H mutation in the RHO gene. The trial will include a single-dose escalation open label arm and a multiple-dose double-blind arm in which a single intravitreal injection of QR-1123 or placebo will be given in one eye. 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, visual field, and optical coherence tomography. Patient reported outcomes will also be evaluated. Patients completing this trial will be able to participate in an extension study if eligible. The trial is designed to be conducted at expert sites in North America and is expected to start in 2019.

Photo: Daniel de Boer, CEO of ProQR

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