ProQR therapeutics recently announced that they have begun enrolling patients for their open-label, exploratory trial PQ-010-002, which will evaluate the effect of their novel investigational therapeutic formulation QR-010 in ∆F508 homozygous (defective gene carrying two allelic copies) and compound heterozygous (defective gene carrying one copy of the ∆F508 mutation and one other disease causing mutation) cystic fibrosis (CF) patients. This trial will seek to estimate QR-010 efficacy after topical administration of the therapy in the nasal mucosa in order to improve the functionality of the Cystic Fibrosis Transmembrane Conductance Receptor (CFTR) protein, a defect in which is the pivotal cause of CF. Efficacy will be measured based on Nasal Potential Difference. NPD is a diagnostic test which measures how well sodium and chloride ions flow across the mucous membranes in the nose.

QR-010 is a unique, first-of-its-kind therapy that may be able to treat the root cause of CF, repairing the genetic mutation in the mRNA of the CFTR gene as a result of the ∆F508 mutation. The PQ-010-002 trial will be a 28-day study conducted in parallel with PQ-010-001 (the ongoing Phase 1b safety and tolerability study of QR-010 in CF patients homozygous for the ∆F508 mutation, where the drug is being delivered to the lungs via inhalation) across 5 sites located in the US and Europe that are experienced in conducting NPD measurements. At least 16 patients with either homozygous or compound heterozygous alleles of the ∆F508 mutation in the CFTR gene are likely to be enrolled and NPD, and sweat chloride measurements are expected to be conducted before and after topical administration of QR-010 on the nasal mucosa three times a week for four weeks.

Noreen R. Henig, MD, Chief Development Officer of ProQR, commented on the study, stating, “This study is an important proof-of-concept study that will test the activity of QR-010 in the treatment of CF. In animal models of CF, QR-010 showed the ability to restore CFTR mediated NPD to normal or wild-type levels. Repeating the same test in individuals with CF will provide an important first signal of the therapeutic potential of QR-010.”

According to John P. Clancy, Professor of Pediatrics and Research Director, Division of Pulmonary Medicine, Cincinnati Children’s Hospital and a member of the Cystic Fibrosis Foundation Therapeutic Development Network’s leadership team, “RNA-based therapeutics are a novel approach to the treatment of the gene mutations that cause CF. The preclinical nasal potential difference studies of QR-010 in the mouse models of CF are quite compelling. The proof-of-concept study of QR-010 will support the understanding of QR-010’s impact on CFTR function in patients with CF with the common ∆F508 CFTR mutation.”