With promising data, ProQR Therapeutics' RNA-based eye drug heads to phase 3

ProQR’s treatment, QR-110, is designed to repair the genetic defect underlying LCA10 in the RNA, which could potentially stop disease progression or even reverse some of its effects. (Rudy and Peter Skitterians)

ProQR Therapeutics reported positive interim data from a phase 1/2 trial of its RNA-based treatment for LCA10, a severe form of blindness caused by a rare genetic disorder. The majority of patients had a “clinically meaningful” improvement in vision after three months of treatment, the data show. The Dutch biotech is submitting a protocol to start a phase 2/3 trial, which could serve as the sole registration trial for the treatment. 

LCA10 is a form of the eye disorder Leber congenital amaurosis that is caused by a p.Cys998X mutation in the CEP290 gene. There is no treatment for LCA10, though Spark Therapeutics markets Luxturna, a gene therapy for LCA2, which is caused by a different mutation. ProQR’s treatment, QR-110, is designed to repair the genetic defect in the RNA, which could potentially stop disease progression, or even reverse some of its effects. 

ProQR screened 12 patients for the phase 1/2 study, ultimately enrolling 10 of them. The open-label trial involved children aged 6 to 17 and adults who have LCA10 due to one or two copies of of the p.Cys998X mutation. Patients in the trial are receiving one injection of QR-110 into the eye every three months for a total of four injections. 

Approximately 60% of them had “rapid and sustained” improvement in vision, as measured by a visual acuity test and their performance on a mobility course. The data were presented at the  International Symposium on Retinal Degeneration in Killarney, Ireland. 

Its data were so promising that it moved up its interim analysis that was originally planned for the six-month mark up to the three-month mark, the company said. 

“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 David Rodman, M.D., who heads up R&D at ProQR. “We observed a clinically meaningful improvement in vision in the treated eye as measured by both mechanistic and potential registration endpoints. Consistent with predictions based on our patient derived optic-cup models, improvement in visual function was observed as early as two months after treatment and was maximal and stable by three months and thereafter. We are very grateful to the study participants, their caregivers, and the investigators and their staff for the support in the development of QR-110 in this trial.” 

ProQR expects to start the phase 2/3 trial in the first half of 2019. The double-blind, placebo-controlled study will take place at sites in North America and Europe, and will enroll 30 to 40 patients. The company will also start testing QR-110 in children younger than six. Because visual impairment from LCA10 begins in infancy, intervening earlier could head off disease progression when it is in its earlier stages. 

Editas Medicine is working on a gene-editing treatment for LCA10, and was expected to be first in the clinic with a CRISPR therapy. But manufacturing issues delayed its timeline from 2017 to 2018, with CEO Katrine Bosley saying in the company’s second-quarter update that it plans to file the IND in October. Editas was pipped at the post last week by CRISPR Therapeutics and Vertex, which started a phase 1 trial for a CRISPR-based beta thalassemia treatment.