Coave Therapeutics released 12-month data from its phase 1/2 trial assessing the safety and efficacy of CTx-PDE6B as a gene therapy treatment for retinitis pigmentosa (RP) caused by bi-allelic mutations in the PDE6B gene (PDE6B-associated RP).
Talk about this company first.
Based in Paris, France, Coave Therapeutics is a clinical-stage biotechnology company developing gene therapies for rare ocular and central nervous system (CNS) diseases.
The company’s adenovirus associated virus (AAV) vector-Ligand Conjugates platform (ALIGATER) is a proprietary technology that allows for targeted delivery, enhanced transduction, and tissue distribution in order to improve the efficacy of its advanced gene therapies.
And the gene therapy candidate?
CTx-PDE6B (AAV2/5-hPDE6B or HORA-PDE6B) is a clinical-stage AAV5-based gene therapy designed to transport a non-mutated copy of the functional human PDE6B gene into the subretinal space. In turn, there is a rapid induction of transgene expression and synthesis of functional PDE6B proteins into the rods and cones of the retina.
By supplying the functional missing protein, the gene therapy is intended to stabilize or block retinal degeneration in patients who are PDE6B deficient.
Now the trial.
The monocentric, open-label, dose-ranging, non-randomized, interventional phase 1/2 clinical trial (NCT03328130) is assessing CTx-PDE6B as a unilateral, subretinal administration in 17 patients (18+ years of age) divided into four cohorts.
To date, CTx-PDE6B has been administered in two ascending doses.
Expand on these cohorts …
Each cohort includes varying doses of CTx-PDE6B:
- Cohort 1 → Low dose (dose-escalation performed following Data and Safety Monitoring Committee [DSMC] assessment)
- Cohort 2a → Medium dose (confirmatory dose determined following DSMC assessment)
- Cohort 2b → High dose (confirmatory dose determined following DSMC assessment)
- Cohort 3 → High dose (confirmatory cohort)
What’s being measured?
The primary outcome measures include the occurrence of ocular and non-ocular adverse events (AEs) over the 12-month time period and followed by 4 years of follow-up.
Secondary outcomes include improvement in:
- Visual function (assessed via mobility test)
- Visual fields (assessed via visual fields measurements)
- Visual function (assessed via reading speed)
- Quality of life [QoL] (measured by the National Eye Institute Visual Function Questionnaire)
Findings?
According to the company, following the 12-month study period, both doses were well-tolerated (n = 17).
A patient subgroup (n = 6) who received a higher dose with a less advanced stage of RP exhibited positive efficacy results based on retinal anatomical evaluation via optical coherence tomography (OCT) and across all five endpoints:
- Best-corrected visual acuity (BCVA)
- Visual field
- Microperimetry
- Full-field sensitivity test
- Mobility tes
What else?
A significant favorable progression of sensitivity for the four central loci within the retina was noted in treated (vs untreated) eyes.
Further, the company reported that the full-field sensitivity test for blue light evaluating rod function illustrated improvement in light perception threshold that favored treated eyes—an observation noted as clinically meaningful.
So what’s next?
According to Coave CEO Rodolphe Clerval: ““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.”