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QR-313 for DEB
QR-313 for dystrophic epidermolysis bullosa received ODD from the FDA in September and ODD from the EMA in November. QR-313 is a first-in-class RNA-based oligonucleotide designed to target the underlying cause of DEB due to mutations in exon 73 of the COL7A1 gene. DEB is a rare genetic disease that can lead to severe blistering of the skin resulting in high treatment burden and poor quality of life for patients with DEB.
In September, positive QR-313 pre-clinical data were presented at the EB2017 Research Conference and ESDR meeting.
IND-enabling studies have been completed and a first in human study of QR-313 in DEB exon 73 patients is expected to commence in 2018. The Phase 1/2 safety and efficacy study is referred to as WINGS (A First in Human, Double-Blind, Randomized, Intra-Subject Placebo-Controlled, Multiple Dose Study of QR-313 Evaluating Safety, Proof of Mechanism, Preliminary Efficacy and Systemic Exposure in Subjects With Recessive Dystrophic Epidermolysis Bullosa (RDEB) due to Mutation(s) in Exon 73 of the COL7A1 Gene). The WINGS study will be conducted in two cohorts: the first cohort will recruit eight RDEB patients with an exon 73 mutation, and a second cohort of DEB patients will be open for enrollment after an interim analysis of the first cohort. The study will evaluate safety, tolerability and pharmacokinetics of QR-313. Interim data from the first trial is expected in 2018, and full results in 2019.
Eluforsen (formerly QR-010) for CF
In April, ProQR was granted two key patents protecting eluforsen in the U.S. and EU which provides the Company with exclusive rights for eluforsen for the treatment of CF until at least 2033. U.S patent no. 9,605,255 is directed to methods of targeting RNA for the most common mutation in CF, called F508del, using oligonucleotides to restore the function of the CFTR protein. In 2016, ProQR was also granted the equivalent European patent (EP 2 852 668 B1). Apart from these ProQR-owned patents, the Company has an exclusive license to U.S. patent no. 9,617,535 from Massachusetts General Hospital covering eluforsen.
The Company presented two abstracts at the European Cystic Fibrosis Conference held in June. Steve Rowe, MD, professor of Pulmonary, Allergy and Critical Care Medicine at University of Alabama and Director of the Gregory Fleming James Cystic Fibrosis Research Center, and Director of the CFF Therapeutics Development Network gave an oral presentation on the final results of study PQ-010-002, a nasal potential difference proof-of-concept study (title “QR-010, an investigational RNA therapeutic, improves CFTR activity in cystic fibrosis subjects homozygous for the F508del mutation”). A poster was also presented on preliminary data from the single ascending dose cohorts of study PQ-010-001, the Company’s Phase 1b safety and tolerability trial (title “QR-010 via inhalation is safe, well-tolerated, and achieves systemic concentrations in a single ascending dose study in subjects with cystic fibrosis homozygous for the F508del CFTR mutation”).
In September, the Company announced positive preliminary top-line results from the multiple-dose cohorts of the Phase 1b randomized, double-blind, placebo-controlled, dose escalation study (Study PQ-010-001) to evaluate the safety, tolerability, pharmacokinetics and exploratory efficacy of eluforsen in adults with CF homozygous for the F508del mutation. A total of 4 dose levels were studied: 6.25, 12.5, 25 and 50 mg of eluforsen administered via inhalation using the PARI eFlow® nebulizer. Patients eligible to participate were males and females of 18 years and over with a ppFEV1 of =70% at time of inclusion, homozygous for the F508del mutation, and not taking CFTR modulator drugs. The study was designed to enroll 8 cohorts of 8 subjects each (6 subjects receiving eluforsen, 2 subjects receiving placebo). In cohorts 1-4, a single dose of eluforsen was administered, and in cohorts 5-8, twelve doses of eluforsen were administered over a 4-week period. In this study, eluforsen was safe and well-tolerated across all dose levels and we believe that eluforsen may have therapeutic benefit for CF patients. Most patients in the trial reported a significant reduction of their CF symptoms after receiving eluforsen (as measured by the validated questionnaire Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score, or CFQ-R RSS) compared to placebo. A supportive trend was observed in the improvement of lung function (as measured by percent predicted forced expiratory volume in 1 second, or ppFEV1) compared to placebo. Subjects that received placebo did not report this reduction in CF symptoms or improvement in lung function. As expected, no changes were observed in sweat chloride and weight gain.
In November, J. Stuart Elborn, Clinical Chair in Respiratory Medicine at Imperial College, Consultant at Royal Brompton Hospital, and immediate past-president of the European Cystic Fibrosis Society, presented data from the Phase 1b trial of eluforsen at the North American Cystic Fibrosis Conference (NACFC). During the conference, the Company also held an investor and analyst event to discuss the Phase 1b data, new opportunities to target other CFTR mutations in the CFTR gene that can potentially be treated using its RNA technologies and potential design of future studies of eluforsen.
ProQR is currently designing a 12-week Phase 2 safety and efficacy study of eluforsen in CF subjects with the F508del mutation. The trial is expected to be conducted at clinical centers in North America, EU and other countries. The Company plans to initiate the trial in 2018 subject to a partnership.