QR-110 demonstrated rapid and sustained improvement in vision in the majority of subjects, as measured by visual acuity and mobility course
QR-110 was well-tolerated with no serious adverse events
A Phase 2/3 pivotal trial is expected to start in the first half of 2019
Management to host a conference call today at
“The results of this interim analysis are encouraging and met our decision criteria to stop enrollment in this study and progress to a pivotal Phase 2/3 trial,” said
Based on the emerging findings from the Phase 1/2 trial, the Company agreed with the
Results from the interim analysis
Efficacy data: Approximately 60% of subjects showed a clinically meaningful response in visual acuity and mobility course endpoints at three months of treatment and there was general concordance across the endpoints. Efficacy signals were observed within two months with maximal benefits seen within two to three months post treatment initiation. A secondary analysis assessing all available data demonstrated that observed effects on efficacy were durable beyond three months.
Visual acuity: In the majority of patients, there was a substantive overall improvement in best corrected visual acuity (BCVA) as assessed by the Berkeley Rudimentary Vision Test (BRVT) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. At three months of treatment, the mean improvement (and standard error of mean, SEM) was -0.67 LogMAR (SEM 0.32) with 62.5% of subjects showing an improvement of greater than -0.3 LogMAR from baseline, which is considered clinically meaningful. The mean change in the contralateral eye was 0.02 LogMAR (SEM 0.05).
Mobility course: Effects on visual acuity correlated with effects on mobility. In the majority of patients there was a substantive overall improvement in functional visual performance as assessed using a series of mobility courses at increasing difficulty and multiple light intensities. At three months of treatment, the mean improvement in navigating the mobility course was 2.6 levels (SEM 1.2) with 57.1% of subjects improving by more than 2.0 levels, which is regarded as clinically meaningful. The mean change in the contralateral eye was 1.36 (SEM 1.04).
Full field stimulus test (FST): Improvements in visual function were supported by a meaningful increase in the ability to detect flashes of red or blue light as determined by the FST. After three months of treatment mean improvement in red light sensitivity was -0.74 log Cd/m2 (SEM 0.35) and improvement in blue light sensitivity was -0.91 log Cd/m2 (SEM 0.38).
Ocular Instability (OCI): Additionally, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients), with a mean change of log -0.14 mm (SEM 0.08) in OCI.
Safety: Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days. So far QR-110 was well tolerated with no serious adverse events related to treatment or procedure. All data and safety monitoring committee (DSMC) reviews were completed with no restrictions on further dose escalation or pediatric dosing.
Start of Phase 2/3 pivotal “ILLUMINATE” trial
The Company has agreed with the
Management will discuss the data during a webcasted conference call today at 8:15 a.m. ET. The live webcast can be accessed here. The dial-in details for the call are +1-877-407-3982 or +1-201-493-6780 (international), conference ID: 13682382.
An archive of the webcast (available for 30 days) can be accessed here.
About the PQ-110-001 Phase 1/2 trial
A total of 12 patients were screened, of which 10 subjects were dosed, have been in the trial for at least one month and are included in the interim analysis. All 10 patients were enrolled in either the 80 μg dose cohort (160 μg loading dose) or 160 μg dose cohort (320 μg loading dose) in the treated eye, with the other eye remaining untreated. Based on the safety profile the DSMC approved further dose escalation if needed. However, given indications of comparable activity in the first two dose groups, the decision was made to defer further dose escalation. Enrollment has been completed and patients in the trial will complete the 12-month treatment and observation period and subsequently will have the option to participate in “INSIGHT”, an open-label extension study including the possibility of receiving treatment in the second eye.
PQ-110-001 is an open-label trial that has been designed to enroll children (age 6 - 17 years) and adults (≥ 18 years) who have LCA10 due to one or two copies of the p.Cys998X mutation in the CEP290 gene. Patients are receiving four intravitreal injections of QR-110 into one eye; one injection every three months. The trial is being conducted at three specialized centers with significant expertise in genetic retinal disease: the
The primary objectives of the PQ-110-001 trial are safety and tolerability. Secondary objectives include pharmacokinetics, as well as restoration/improvement of visual function and retinal structure through ophthalmic endpoints, such as visual acuity (BCVA), mobility course, full field stimulus testing (FST), ocular instability (OCI), optical coherence tomography (OCT), and pupillary light reflex (PLR). Changes in quality of life in the trial subjects are also being evaluated.
QR-110 is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of Leber’s congenital amaurosis 10 due to the p.Cys998X mutation (also known as the c.2991+1655A>G mutation) in the CEP290 gene. The p.Cys998X mutation is a substitution of one nucleotide in the pre-mRNA that leads to aberrant splicing of the mRNA and non-functional CEP290 protein. QR-110 is designed to restore normal (wild-type) CEP290 mRNA leading to the production of normal CEP290 protein by binding to the mutated location in the pre-mRNA causing normal splicing of the pre-mRNA. QR-110 is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in
About Leber’s Congenital Amaurosis 10
Leber’s congenital amaurosis (LCA) is the most common cause of blindness due to genetic disease in children and consists of a group of diseases of which LCA10 is the most frequent and one of the more severe forms. LCA10 is caused by mutations in the CEP290 gene, of which the p.Cys998X mutation is the most common. LCA10 leads to early loss of vision causing most people to lose their sight in the first few years of life. To date, there are no treatments approved or other products in clinical development that treat the underlying cause of the disease. Approximately 2,000 people in the Western world have LCA10 because of this mutation.
This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Such statements include those relating to QR-110 and the clinical development and therapeutic potential thereof, including our PQ-110-001 clinical trial of QR-110 and statements regarding release of clinical data, including that from our PQ-110-001 trial. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the
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Source: ProQR Therapeutics N.V.