eyeDNA plans pivotal trial of retinitis pigmentosa therapy

Two-year data with eyeDNA Therapeutics’ gene therapy for retinitis pigmentosa (RP), an inherited form of blindness, has prompted the biotech to seek discussions with regulators about the design of a pivotal trial.

The new results, presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 meeting in Seattle, USA, suggest that the therapy achieved improvements in vision and may slow down the progression of RP, according to eyeDNA, a newly formed subsidiary of France’s Coave Therapeutics.

Approximately 100,000 people in the US and an estimated 2 million people worldwide suffer from RP, a condition that results in progressive damage to light-detecting cells in the retina and is the leading cause of inheritable blindness.

eyeDNA’s phase 1/2 study is focusing on patients with a specific form of RP caused by mutations in the PDE6b gene, which one study estimated to account for around 1.4% of autosomal recessive RP cases.

The HORA-PDE6b therapy, which delivers a replacement copy of the unmutated gene using an AAV5 viral vector, was administered into one eye of patients in the trial to allow a comparison with the other untreated eye.

To date, HORA-PDE6b has been administered in 17 evaluable adult patients, of whom six received the highest of four doses of the therapy. In this group, the treatment led to improvements in best corrected visual acuity (BCVA) measured on an eye chart compared to the untreated eye at 24 months, reinforcing 12-month data reported last year.

There was also a smaller decrease with the gene therapy in the Goldmann visual field (GVF) measure – which assesses how far up, down, left, and right an eye can see without moving – and an improvement of the light perception threshold in favour of the treated eyes measured using full-field stimulation testing (FFST).

From a safety perspective, the therapy was associated with five adverse effects affecting the eye that were deemed serious, including a case of reduced visual acuity and an inflammatory response (chorioretinitis) that may have been linked to the treatment. Both have since been resolved.

“[This] data will support our discussions with regulators to determine the optimal route for getting HORA-PDE6b to patients,” said Rodolphe Clerval, eyeDNA’s chief executive.

“At the same time, we continue to evaluate HORA-PDE6 in an expansion cohort of younger patients with less advanced disease, for whom treatment with HORA-PDE6b could have an even greater therapeutic impact.”

The company is one of several working on gene therapies for RP, a family of progressive and irreversible diseases that lead to significant visual impairment and blindness. Thousands of mutations across more than 50 genes have been associated with RP.

Ocugen’s NR2E3-directed OCU400, Beacon Therapeutics’ AGTC-501 for an X-linked form of the disease, and Frontera Therapeutics’ RPGR replacement FT-002 are all in pivotal clinical trials.

Another approach is being taken with Nanoscope Therapeutics and its MCO-010 (sonpiretigene isteparvovec) gene therapy, which attempts to treat patients with RP regardless of the underlying mutation and recently generated encouraging results in a phase 2b trial.

At the moment, Roche/Spark Therapeutics’ Luxturna (voretigene neparvovec) is the only approved gene therapy for an inherited retinal disease and is indicated for a small subpopulation of patients with the RPE65 gene mutation, estimated to represent 1% or less of all cases of retinal dystrophy.

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