ProQR Announces Updates and Priorities After Illuminate Trial Analyses

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ProQR Therapeutics completed an in-depth strategic review to prioritize its objectives toward advancing RNA therapies, following news that its Illuminate Phase 2/3 clinical trial of sepofarsen in LCA10 CEP290 did not meets its primary endpoint of improving visual acuity.

The Dutch-based biotechnology company delivered an update on its sepofarsen program after a comprehensive analysis of data from the Illuminate trial and it announced a corporate restructure and workforce reduction. 

Based on information from the review, ProQR will prioritize two strategic objectives dealing with genetic eye disease and RNA editing technology.

The company plans to explore a development path for selected genetic eye disease programs subject to regulatory feedback from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).

Regarding RNA editing technology, ProQR will accelerate development of the Axiomer® RNA editing technology platform and pipeline activities expanding into areas beyond the eye, including initially the liver and central nervous system. The technology aims to correct disease-causing genetic mutations and reverse the underlying course of currently untreatable diseases.

Daniel A. de Boer, Founder and CEO of ProQR Therapeutics, said in a statement: “We are focusing our strategy on accelerating our Axiomer® RNA-base editing platform technology and a select pipeline of RNA therapies for inherited retinal diseases  (IRDs) as we remain committed to developing RNA therapies for patients with high unmet need.” 

Corporate Reconstruction and Priorities

ProQR also plans to reduce expenses by making program priorities, changing its corporate structure, and reducing its workforce by a third. 

The company will focus its ultevursen QR-421a program for USH2A-mediated Usher syndrome and retinitis pigmentosa (RP) on a single Phase 2/3 Sirius trial, with the potential of an interim/futility analysis next year. 

ProQR is suspending all other research for IRDs, including its QR-1123 program for autosomal dominant RP and its QR-504a program for Fuchs endothelial corneal dystrophy.

The business also will reduce its workforce by about 30 percent, including the departure of its Chief Scientific Officer Naveed Shams, MD, PhD.

 Co-Founder and Supervisory Board Chair Dinko Valerio said in a statement: 

“We believe deeply in the promise of RNA therapies, the Company’s pioneering efforts in this field, and ProQR employees. These are the right steps to take to offer the best opportunity to create long-term value for all of our stakeholders, including our shareholders whom we thank for their support, and the communities we aim to serve.” 

De Boer thanked the people leaving the company for their significant contributions toward the company’s mission. He characterized the changes as extremely difficult decisions necessary to drive long-term growth and value. 

“I also want to acknowledge the disappointment that many in the eye disease community may feel today, particularly individuals and families living with autosomal dominant retinitis pigmentosa and Fuchs endothelial corneal dystrophy as we wind down our programs for these indications.”

Sepofarsen Update 

Following the top-line data announcement in February that Illuminate, ProQR’s pivotal Phase 2/3 trial of sepofarsen in LCA10, did not meet the primary endpoint of Best Corrected Visual Acuity (BCVA) at month 12, compared to a sham procedure control group, comprehensive analyses revealed no technical errors in the trial conduct, data handling, or the medicine product used. 

The overall safety profile of sepofarsen was consistent with earlier trials. When the effect in the sepofarsen treated eye was compared to the untreated eye in the same patient, at month 12, a benefit in vision was observed. This effect was not observed in the control group that received a sham treatment.

Overall, the post-hoc analyses showed that the efficacy seen with sepofarsen when comparing the active treatment and sham eyes to their corresponding untreated contralateral eyes across BCVA, Full Field Stimulus Test (FST), and other endpoints is more consistent with the results seen in earlier trials, where the untreated contralateral eye was used as the control.

Based on these results, ProQR will focus on core activities related to sepofarsen. The company plans to meet with the EMA and FDA to discuss these data from the Illuminate trial and share an update later this year.

ProQR currently plans to continue Illuminate, which is a two-year study, the Brighten pediatric study, and the Insight open-label extension study, until further regulatory guidance.

Aniz Girach, MD, Chief Medical Officer of ProQR Therapeutics, said in a statement: 

“While we were disappointed by the outcome of the primary analysis, we believe that these post-hoc analyses and the observation that approximately a third of the patients benefited across multiple concordant endpoints in this trial, in combination with the high unmet need in LCA10, warrants a discussion with the regulators.”

Data from the Illuminate trial will be presented at the annual Retinal Cell and Gene Therapy Innovation Summit on April 29, 2022, and at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting from May 1-4, 2022. 



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