Shares of ProQR Therapeutics (PRQR) skyrocketed 51% on news that the trial returned positive results. The company is dedicated to changing lives through the creation of transformative RNA therapies for inherited retinal diseases (IRDs), today announced results from a planned analysis of its Phase 1/2 Stellar trial of QR-421a in adults with Usher syndrome and non-syndromic retinitis pigmentosa (nsRP) due to USH2A exon 13 mutations.
In the trial, QR-421a demonstrated benefit on multiple measures of vision that moved in concordance, including visual acuity, visual fields, and optical coherence tomography (OCT) retinal imaging, after a single dose. QR-421a was observed to be well tolerated with no serious adverse events reported. Based on these findings, the Company plans to advance QR-421a to two parallel pivotal Phase 2/3 trials by year end 2021 – one in early-moderate patients, one in advanced patients.
QR-421a was observed to be well tolerated at all doses. There were no serious adverse events reported and no inflammation was observed. One patient had worsening of pre-existing cataracts in both the treated and untreated eyes; both were deemed not treatment related by the investigator. One patient had progression of pre-existing cystoid macular edema (CME) that was managed with standard of care. Both cataracts and CME are associated with a high rate of occurrence in the natural history of this disease.
Given the key differences in baseline characteristics, patients were categorized into “advanced” and “early-moderate” populations based on baseline visual acuity.
In advanced patients, the primary measure of efficacy is BCVA. In early-moderate patients, the primary measure of efficacy is measurement of visual fields by static perimetry. QR-421a-treated patients responded on endpoints consistent with their disease stage in both advanced and early-moderate patient populations after a single injection.
All three doses studied in the Stellar trial were observed to be active as predicted by the pre-clinical data. No differences were observed based on patients being homozygous or heterozygous, or having Usher syndrome or non-syndromic retinitis pigmentosa. These findings are consistent with the preclinical data for QR-421a.
What this means for PRQR investors
Based on the findings, the company will now proceed with pivotal trials in centers of excellence. In addition, the company will conduct a Sirius trial in which it will be for the advanced population. The trial will be administered every 6 months, the preliminary design for Sirius is a double-masked, randomized, sham-controlled, 24-month, multiple-dose study. The trial is expected to enroll approximately 100 adults with Usher syndrome and nsRP due to USH2A exon 13 mutations, including both homozygous and heterozygous patients.
In parallel to Sirius, the Company plans to start the “Celeste” Phase 2/3 trial in early-moderate patients. The preliminary design for Celeste is a double-masked, randomized, sham-controlled, 24-month, multiple-dose study. The trial is expected to enroll approximately 100 adults with Usher syndrome and nsRP due to USH2A exon 13 mutations. The primary endpoint in this trial will be based on static perimetry at 18 months, with potential for an earlier interim analysis. In this three-arm study, two different doses will be studied that will be administered every 6 months, and a third arm will receive sham treatment.