ProQR Completes Enrollment for Next Phase of RNA Therapy for LCA10-CEP290

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ProQR Therapeutics reached an important milestone by completing enrollment in the next pivotal phase of clinical trials of sepofarsen, a developing RNA therapy for treating LCA10, a form of Leber congenital amaurosis (LCA) with a mutation in the CEP290 gene

The biotechnology company based in Boston and in Leiden, The Netherlands, announced earlier this month that it finished enrollment in its Phase 2/3 Illuminate study of sepofarsen for treatment of LCA10 due to the p.Cys998X mutation in the CEP290 gene. 

LCA10 is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life. The mutation affects about 2,000 people in the Western world

Sepofarsen is an antisense oligonucleotide (AON)  that works like “genetic tape” to fix the mutation. The therapy is unlike gene replacement therapies in which whole genes are delivered to replace defective copies. 

The drug aims to repair the genetic defect that causes the disease in the ribonucleic acid (RNA). The mutation leads to an aberrant splicing of a person’s messenger RNA (mRNA) and leads to a non-functional CEP290 protein. Sepofarsen is designed to enable normal splicing, resulting in subsequent production of functional CEP290 protein. 

Recruiting patients for clinical trials represents one of the biggest challenges in getting studies underway. The COVID-19 pandemic and concerns about spreading the virus presented an unprecedented challenge in and of itself. Pharmaceutical companies also have steered their focus from studies across the board as they raced toward developing and rolling out worldwide virus vaccines. 

Finding the required 33 LCA10 individuals for the Illuminate trial in a subset of a people with a rare condition was exceptionally challenging, and ProQR exceeded that requirement by enrolling 36 participants.

During the Phase 2/3 study, the 36 patients, ages 8 and older, are set to receive sepofarsen either in a dose expected to be used once the drug gains approval or a lower dose or a placebo. The 12-month clinical trial is intended to support an application for marketing approval of sepofarsen. The study is being conducted in the United States, Canada, Brazil, The Netherlands, Belgium, France, Italy, Germany, and the United Kingdom.

The drug is administered through intravitreal injections in the eye. It is also a platform for use as transformative therapies for treating Usher syndrome and retinitis pigmentosa (RP)

Top-line results in early 2020 from the Phase 1/2 clinical trial of sepofarsen in 11 children and adults revealed that 60 percent of patients had improvements in visual acuity and navigating a mobility course. The study, carried out in the United States and Belgium, also netted a super responder, a person who responded particularly well to the treatment. 

Laura Manfre, chair and co-founder of Sofia Sees Hope, said that as the parent of a child with an LCA diagnosis, she was told there was nothing that could be done and that her family needed to accept that their daughter would one day be blind.

“Now, in early clinical testing we have seen the potential for sepofarsen to make a significant difference for patients with LCA10 due to a mutation in the CEP290 gene,” she said. “We see hope for individuals living with this disease. We look forward to learning about the results of the Illuminate trial and continuing to work with ProQR as they advance their pipeline of RNA therapies to potentially help children, adults, and families who are affected by blindness caused by LCA and other rare inherited retinal diseases.”

Aniz Girach, MD, ProQR’s chief medical officer, said in a statement that the company was pleased to have completed enrollment of the Illuminate trial of sepofarsen.

“This marks an important milestone for ProQR, as well as for the LCA10 and broader inherited retinal disease community,” Girach said. “In surpassing our enrollment target, we were able to accommodate the broad interest to participate in the trial. This speaks to the fact that there are currently no approved treatments for patients with LCA10.

“If approved, sepofarsen has the potential to be the first therapy to address this high unmet medical need for patients who would otherwise face blindness, he said. 

“We are grateful to those who have supported our efforts in bringing this trial forward, including our investigators, patients, and caregivers. We look forward to sharing the top-line results in the first half of 2022.”