Coave shares positive 12-month results from Phase I/II trial of CTx-PDE6b for retinitis pigmentosa


This positive data supports Coave’s preparations for a registrational trial with CTx-PDE6b in this indication.

©Siarhei /

This positive data supports Coave’s preparations for a registrational trial with CTx-PDE6b in this indication. (Image Credit: Adobe Stock/Siarhei)

Coave Therapeutics shares the positive 12-month results from its Phase I/II trial regarding the safety and efficacy of CTx-PDE6b for retinitis pigmentosa (RP) caused by bi-allelic mutations in the PDE6B gene (PDE6b RP). This innovative gene therapy, generated positive data supporting Coave’s preparations for a registrational trial with CTx-PDE6b in this indication.

The company added in its news release it has received regulatory approval to expand the ongoing trial to include a new cohort of 6 younger patients (aged 13-25 years) with earlier stages of disease to further explore the clinical benefit of CTx-PDE6b in a broader patient population. The first patient is expected to receive treatment by July 2023.

Coave noted in its news release CTx-PDE6b is a clinical-stage, AAV5-based gene therapy for the treatment of retinitis pigmentosa (RP) caused by bi-allelic mutations of the PDE6b gene (PDE6b RP). RP is a type of inherited retinal dystrophy that leads to blindness by midlife and is characterized by a progressive loss of photoreceptors. There are currently no approved treatments for PDE6b RP.

The company also noted CTx-PDE6b is designed to deliver a full-length non-mutated copy of the functional human PDE6b gene into the subretinal space where it rapidly induces robust transgene expression and synthesis of functional PDE6b protein in photoreceptive rod cells. By providing these cells with the functional missing protein, CTx-PDE6b is expected to stabilize or halt retinal degeneration in PDE6b-deficient patients.

Moreover, CTx-PDE6b (AAV2/5-hPDE6B or HORA-PDE6b) is being evaluated in a Phase I/II, monocentric, open-label, dose-ranging clinical trial (NCT03328130) to assess its safety and efficacy in patients with PDE6b retinitis pigmentosa (RP). Seventeen patients aged 18 years and above across 3 cohorts and 2 doses have completed the 12-month study period. The study will now enroll a further cohort of 6 patients aged 13-25 years with earlier-stage disease.

To date, CTx-PDE6b has been administered to 17 patients aged 18 years and older presenting an advanced form of PDE6b RP using two ascending doses. The treatment was administered in the more affected eye while the other eye served as an untreated control.

Following the 12-month study period, both doses were well tolerated (n=17). A subgroup of patients (n=6) with less advanced disease who received the higher dose showed positive efficacy results, consistently measured across all 5 clinical endpoints (BCVA - Best Corrected Visual Acuity, Visual Field, Microperimetry, Full Field Sensitivity Test and Mobility test) and the retinal anatomical evaluation by OCT (Optical Coherence Tomography). In this sub-group, using microperimetry, a significant favorable progression of sensitivity of the 4 central loci of the retina was observed in the treated eyes compared to the untreated eyes.

The company added in the release the full-field stimulation test in blue light assessing rod function shows an improvement of the light perception threshold in favor of the treated eyes, which is considered clinically meaningful.

These data support a positive effect of CTx-PDE6b on visual functions and provide a strong rationale to pursue the product’s clinical development with the preparation of a registrational trial.

The Phase I/II study design and data will be presented at upcoming conferences.

Rodolphe Clerval, CEO of Coave, said the company is encouraged by the safety and efficacy data observed so far in patients who have been treated with CTx-PDE6b.

“This therapy has shown a good safety profile and promising benefit in visual functions within the treated eye after a 12-month follow-up period,” Clerval said in the news release. “These initial findings provide strong support for expanding this Phase I/II study to include patients with less advanced disease while we begin our preparations for a registrational trial with CTx-PDE6b.”

Michel Weber, MD, PhD, a professor at Nantes University Hospital (France) and Guylène Le Meur, MD, PhD, MCU-PH, associate professor and head of Ophthalmology at Nantes University Hospital, added PDE6B retinitis pigmentosa is a progressive and irreversible inherited degenerative disease that leads to significant visual impairment and blindness.

“These initial safety and promising efficacy results are of great medical interest and could represent a significant step towards providing a specific treatment for patients with this devastating disease,” Weber said in the news release.

Coave added in the news release it is responsible for the global development of CTx-PDE6b and retains commercial rights to the product in the US, Japan, South Korea, China and other territories outside Europe. In Europe and certain other countries, CTx-PDE6b is being co-developed by Coave and Théa Open Innovation (‘TOI’) under a license and development agreement with exclusive rights granted to TOI to commercialize CTx-PDE6b in these territories.

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