Research update – ProQR

Posted on: Friday 22 April 2022



In February this year, ProQR announced a disappointing outcome for their phase 2/3 trial of sepofarsen for Leber congenital amaurosis type 10 (LCA10). These results prompted ProQR to undertake a strategic review of their activity, alongside an in-depth analysis of the sepofarsen trial data.

Sepofarsen update

Additional analysis of the clinical trial data has offered some encouragement.

The earlier top line data suggested that the treatment did not meet the primary endpoint of improved Best Corrected Visual Acuity (BCVA, measured by reading letters from an eye chart) at month 12 compared to a sham procedure control group (individuals who did not get sepofarsen at all but underwent a “fake” procedure in one eye). The inclusion of this sham procedure control group was a requirement of the US regulatory agency (the FDA) for any future licensing application, but was not demanded by the European agency (the EMA), who prefer to look at a comparison between the treated eye and untreated eye in the same person.

Further analysis has shown that when the effect of sepofarsen on the treated eye was compared to the untreated eye in the same individual, at month 12, a benefit in vision was observed. These findings were supported by the patient reported outcomes analysis, which demonstrated that 61% of participants in the treatment groups reported an improvement in vision.

These results are more consistent with the earlier phases of clinical testing and suggest that the treatment does show promise. ProQR has therefore decided to continue progressing with the sepofarsen clinical trials for now, and in the meantime will meet with both the FDA and the EMA later this year to discuss the data. After further guidance from the regulators, ProQR will share an update before the end of 2022.

ProQR strategic review

As a result of their strategic review, the company has now announced the following next steps:

  • Continuation of a single phase 2/3 trial of ultevursen (QR-421a) for USH2A-mediated Usher syndrome and retinitis pigmentosa. This trial is already underway, with a possible interim analysis in 2023.
  • Suspension of development of QR-1123 for autosomal dominant retinitis pigmentosa involving the RHO gene. (This product was at an earlier phase of clinical testing.)
  • Suspension of all other IRD-related research activities.
  • Reduction of the workforce by approximately 30%.

Daniel A. de Boer, Founder and CEO of ProQR Therapeutics, said: “These have been extremely difficult decisions to make as we position the business to drive long-term growth and value. I want to thank the employees separating from ProQR for their significant contributions toward our mission. 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… as we wind down our programs for these indications.”

Other adRP news, away from ProQR …

Biotechnology company Ocugen has begun a phase 1/2 clinical trial in the USA that will include some participants with RP caused by autosomal dominant mutations in the RHO gene. Ocugen’s gene therapy candidate, known as OCU400, aims to increase production of a substance that could stabilise retinal cells and limit further photoreceptor degeneration. The company believes that OCU400 may have the potential to work for a large number of different underlying genetic causes of RP. For now, their early stage trial will include participants with mutations in the RHO and NR2E3 genes.