EyeDNA Reports Positive 24-Month Data for HORA-PDE6b Gene Therapy in Retinitis Pigmentosa Trial

May 7, 2024 – eyeDNA Therapeutics (‘eyeDNA’), a subsidiary of Coave Therapeutics, a genetic medicine company, has announced promising 24-month follow-up data from its Phase I/II study (NCT03328130) assessing the safety and efficacy of HORA-PDE6b. This investigational gene therapy targets retinitis pigmentosa (RP) caused by bi-allelic mutations in the PDE6b gene (PDE6b RP). These findings were shared during an oral presentation on May 6 at the Association for Research in Vision and Ophthalmology (ARVO) 2024 meeting in Seattle, WA, US.

The 24-month follow-up results reaffirm the positive outcomes observed in the 12-month interim analysis and support the preparation for a registrational trial for HORA-PDE6b in PDE6b RP patients. Discussions with health authorities in the US and Europe are anticipated to chart the optimal pathway for making HORA-PDE6b available to patients with PDE6b RP.

So far, HORA-PDE6b has been administered to 17 patients, aged 18 years and older, presenting an advanced form of PDE6b RP. The gene therapy was administered in the more affected eye, with the untreated eye serving as a control. Among six patients who received a high dose and had less advanced disease (Best Corrected Visual Acuity [BCVA] score ≤75 ETDRS letters, Goldmann Visual Field [GVF] ≥ 10 degrees), positive efficacy results were observed at 24 months. The BCVA mean change from baseline improved by +0.09 LogMar in the untreated eye, while the treated eye's acuity remained stable (+0.02 LogMar). The mean reduction in GVF area was over 300 deg² greater in the untreated eyes compared to the treated eyes.

Additionally, long-term follow-up data from seven patients in the low dose group over five years indicated a consistent decline in BCVA of the untreated eyes (increase of 0.05 to 0.08 LogMAR/year from the second year), aligning with the natural progression of the disease. Meanwhile, the BCVA of the treated eyes stabilized (between +0.03 and +0.06 LogMAR over the same period). The BCVA difference between treated and untreated eyes at five years was 0.25 LogMAR (12 Letters).

The full-field stimulation test (FFST) in blue light, which evaluates rod function, showed an improvement in light perception threshold in favor of the treated eyes, deemed clinically meaningful (improvement of almost six decibels). Positive trends in retinal anatomical evaluation by Optical Coherence Tomography (OCT; Ellipsoid Zone horizontal length) observed at the 12-month follow-up persisted after 24 months.

Throughout the 24-month study, both dosing levels were well tolerated among the 17 patients. There were five ocular Serious Adverse Events (SAEs), including two possibly related to HORA-PDE6b (one case of chorioretinitis and one of reduced visual acuity), both of which were resolved. Notably, patients did not receive preventive oral corticosteroids.

A new cohort involving four to six younger patients aged 13-17 years, with a baseline GVF ≥ 20 degrees in each meridian and at an earlier disease stage, is ongoing, with three patients enrolled.

Rodolphe Clerval, Chief Executive Officer, expressed optimism about the data, stating, "The highly encouraging safety and efficacy data observed in patients two years after treatment with HORA-PDE6b continue to support our view that this novel gene therapy could provide an important clinical benefit for PDE6b RP patients. These data will support our discussions with regulators to determine the optimal route for getting HORA-PDE6b to patients.” 

Dr. Jean-Baptiste Ducloyer of Nantes University Department of Ophthalmology added, "PDE6b retinitis pigmentosa is a progressive and irreversible inherited degenerative disease that leads to significant visual impairment and blindness. These two-year safety and promising efficacy results are of great medical interest and could represent a significant step towards providing an effective treatment for patients with this devastating disease."

eyeDNA Therapeutics, a subsidiary of Coave Therapeutics, is committed to developing transformative gene therapies for inherited retinal disorders. Their lead program, HORA-PDE6b, is undergoing evaluation in a Phase I/II trial for retinitis pigmentosa caused by PDE6b gene mutations.

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