RNA Therapeutics from ProQR Therapeutics lose It’s a key test for an inherited eye disease and an unexpected setback for the biotech’s most advanced project. According to preliminary results, patients who received the experimental treatment sepofarsen showed little difference compared to the control group.
A phase 2/3 study in patients with Leber congenital amaurosis also failed to assess secondary objectives of other measures of visual acuity. ProQR, based in Leiden, Netherlands, said it will continue to analyze the data and provide more details at future medical meetings. On Friday’s conference call, CEO Daniel de Boer expressed surprise and disappointment with early data from a trial called ILLUMINATE.
“We will figure out what happened with the sepofarsen ILLUMINATE trial, and we will spare no effort,” de Boer said.
Leber congenital amaurosis (LCA) is a disease in which retinal photoreceptors degenerate or malfunction. The disease stems from a genetic mutation; defects in the CEP290 gene cause the most common and severe form, called LCA10. People born with LCA10 usually lose sight in the first few years of life. There is no cure for the underlying cause of the disease.
ProQR is designed to treat LCA10 by correcting the genetic defect that causes it. Sepofarsen is an RNA therapy designed to restore the ability of the CEP290 gene to produce functional CEP290 protein. The treatment comes from the ProQR platform technology, which has resulted in five programs, all of which inherit retinal diseases that the biotech aims to treat with RNA therapy injected into the eye.
sepofarsen’s pivotal Phase 2/3 trial enrolled 36 patients aged 8 years or older who were genetically confirmed to have LCA10 due to a CEP290 mutation. The patients were randomly assigned to one of three groups: a low or high dose of sepofarsen, or a third group to receive a sham procedure with a mock injection.
The primary objective of the study was to measure best-corrected visual acuity according to widely used visual acuity assessments, where negative scores indicate improvement and positive scores indicate worsening. At the 12-month mark, the mean change from baseline in best visual acuity was -0.11 in the high-dose group and -0.13 in the low-dose group, ProQR said. In the group of patients who underwent sham surgery, the mean change in score was -0.12.
Secondary study endpoints included the full-field stimulus test, which is a measure of the lowest flashes of light that elicited a visual stimulus, and performance on a moving course. On these measures, ProQR also reported no differences between the treated and sham groups.
No serious adverse events were reported in the study, and patients tolerated the RNA therapy well. Chief Medical Officer Aniz Girach said cataracts, cystoid macular edema and retinal thinning were observed; these findings are consistent with those reported in the sepofarsen Phase 1/2 trial. In the study, which included five children and six adults, ProQR reported “rapid and sustained improvements in vision” in most patients, paving the way for a pivotal Phase 2/3 study. De Boer said the 12-month data reported Friday was the first result of the three-year study, which will continue. Responding to an analyst’s question about the need for another sepofarsen study, de Boer said ProQR won’t know until the company has a better understanding of the results of the current study.
“Everything is on the table,” De Boer said. “Once we have completed this analysis, we can get back to you.”
At the end of the third quarter of 2021, ProQR reported a cash position of 156.1 million euros, which the company estimates is sufficient to support operations through mid-to-late 2024. Between now and then, ProQR will continue to advance its other RNA therapeutics. last year, ProQR reports positive Phase 1/2 data for ultevursen, an RNA therapy for Usher syndrome and retinitis pigmentosa. The therapy is now in Phase 2/3 testing. Another ProQR program, QR-504a, is in early clinical development for Fuchs type 3 endothelial corneal dystrophy. Both studies are expected to report data later this year.
ProQR also continues to develop its Axiomer technology platform, which supports RNA editing. Although ProQR will use the technology to develop treatments for inherited eye diseases, the company is open to partnerships with companies interested in applying the technology to other therapeutic areas. In collaboration with Eli Lilly, ProQR is using Axiomer to develop drugs for up to five targets in the liver and central nervous system.
De Boer dismissed suggestions that sepofarsen’s early stage 2/3 results in LCA10 affect the company’s other projects. ProQR has seen consistent results, leading to clinical testing and expanded studies of multiple molecules produced by its technology, he said.
“In our view, the outliers here are the ILLUMINATE results that we represent today,” he said. “So we remain confident in the platform itself.”
Investors did not share De Boer’s optimism. Shares of ProQR fell more than 75% on Friday to about $1.37 a share.
Photo: optical memoryGetty Images
