Clinically meaningful benefit in visual functions and
good safety profile of HORA-PDE6b is confirmed at 24-month
follow-up
Phase
I/II results will be discussed with US and European health
authorities to define optimal path to making HORA-PDE6b available
to patients with PDE6b Retinitis Pigmentosa
Paris, France, May 7, 2024 –
eyeDNA Therapeutics (‘eyeDNA’), a newly created subsidiary of Coave
Therapeutics (‘Coave’), a genetic medicine company focused on
developing life-changing therapies, today announces positive
24-month follow-up results from its Phase I/II study (NCT03328130)
evaluating the safety and efficacy of HORA-PDE6b, its
investigational gene therapy for retinitis pigmentosa (RP) caused
by bi-allelic mutations in the PDE6b gene (PDE6b RP). These data
were reported during an oral presentation* on May 6, at the
Association for Research in Vision and Ophthalmology (ARVO) 2024
meeting in Seattle, WA, US.
The positive 24-month follow-up data presented
confirm results from the previous interim analysis of the trial
conducted at the 12-month follow-up point and support preparation
for a registrational trial for HORA-PDE6b in PDE6b RP patients.
Further discussions with health authorities in the US and Europe
are planned to define the optimal path to making HORA-PDE6b
available to PDE6b RP patients.
To date, HORA-PDE6b has been administered in 17
evaluable patients aged 18 years and older presenting an advanced
form of PDE6b RP using two ascending doses in four consecutive
cohorts. The treatment was administered in the more affected eye
while the other eye served as an untreated control.
In a subgroup of clinical interest of six
patients receiving the high dose, with less advanced disease (Best
Corrected Visual Acuity (BCVA) score ≤75 ETDRS letters [ ≤ 20/32
Snellen equivalent], Goldmann Visual Field (GVF) ≥ 10 degrees),
positive efficacy results were reported at 24 months on the BCVA
and the GVF outcomes. The BCVA mean change from baseline increased
by +0.09 LogMar in the untreated eye, while acuity in the treated
eye was stabilized (+0.02 LogMar). From baseline, the mean
reduction of the GVF was over 300 deg² superior in the untreated
eyes compared to the treated eye.
Interestingly, long-term data available from
patients from the low dose group (n=7) followed up over a five-year
period found that the BCVA of the untreated eyes consistently
declined (increase of 0.05 to 0.08 LogMAR/year from the second
year), which is in line with the natural history of the disease.
Meanwhile, the mean change from baseline of BCVA of the treated
eyes in the same group is stabilized (between +0.03 and +0.06
LogMAR over the same follow-up period). The difference of BCVA mean
change from baseline between the treated eyes and the untreated
eyes at five years is 0.25 LogMAR (12 Letters).
Furthermore, the full-field stimulation test
(FFST) in blue light assessing rod function continues to show an
improvement of the light perception threshold in favor of the
treated eyes, which is considered clinically meaningful
(improvement of almost six decibels). The interesting positive
trend on the retinal anatomical evaluation by Optical Coherence
Tomography (OCT; Ellipsoid Zone horizontal length) observed at
12-month follow-up on the subgroup of clinical interest is
maintained after 24 months.
Following the 24-month study period, both doses
were well tolerated (n=17). Five ocular Serious Adverse Events
(SAEs) occurred including two resolved SAEs possibly related to
HORA-PDE6b (one chorioretinitis and one reduced visual acuity).
Patients did not receive preventive oral corticosteroids.
An additional cohort of four to six younger
patients aged 13-17 years old with a GVF at baseline ≥ 20 degrees
in each meridian and at an earlier disease stage is ongoing with
three patients enrolled.
“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,” said
Rodolphe Clerval, Chief Executive Officer. “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.”
“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,”
commented Dr. Jean-Baptiste Ducloyer, MD, Nantes University
Department of Ophthalmology.
*Abstract
2134:
JB Ducloyer, et al. 12-month Safety and Efficacy
Evaluation of HORA-PDE6b, a Gene Therapy Targeting Patients with
Retinitis Pigmentosa Due to Biallelic PDE6B Gene Mutation
***
About eyeDNA Therapeutics and
HORA-PDE6b
eyeDNA Therapeutics, a wholly owned subsidiary
of Coave Therapeutics, is a clinical-stage gene therapy company,
focused on developing life-changing therapeutics for inherited
retinal disorders. Our lead program HORA-PDE6b, an AAV5-based gene
replacement therapy, is being evaluated in a Phase I/II trial for
the treatment of retinitis pigmentosa (RP) caused by bi-allelic
mutations of the PDE6b gene (PDE6b RP) (NCT03328130).
eyeDNA and Théa Open Innovation (‘TOI’) are
partners for the development and commercialization of HORA-PDE6b.
eyeDNA is responsible for the global development of HORA-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, HORA-PDE6b is being co-developed by Coave
and TOI under a license and development agreement with exclusive
rights granted to TOI to commercialize HORA-PDE6b in these
territories.
About Coave
Therapeutics
At Coave Therapeutics, we are leading the
transition of genetic medicine from rare to prevalent conditions,
starting with neurodegenerative and eye diseases. Our proprietary
ALIGATER™ (Advanced Vectors-Ligand Conjugates) platform introduces
chemical modifications onto AAV capsids or Lipid Nanoparticles
(LNPs) to overcome the limitations of current vectors on efficacy,
safety, and manufacturability.
With low doses and optimized routes of
administration, our conjugated vectors have demonstrated markedly
improved transduction and biodistribution in the central nervous
system and the eye across different species. Our diverse pipeline
of novel genetic medicines can potentially transform the lives of
people afflicted by rare and prevalent neurodegenerative and ocular
diseases – including genetically and non-genetically defined
indications.
Coave recently created its subsidiary eyeDNA
Therapeutics to focus on the development – up to the marketing
authorization application – of its unique gene therapy HORA-PDE6b
for the treatment of inherited retinal diseases caused by mutations
in the human PDE6b gene.
Headquartered in Paris, France, Coave
Therapeutics is backed by leading international life sciences
investors. For more information about the science, pipeline, and
people, please visit https://coavetx.com/ and follow us on
LinkedIn.
CONTACTS eyeDNA
Therapeutics and Coave Therapeutics Rodolphe Clerval,
CEO contact@coavetx.com
MEDiSTRAVA Sylvie Berrebi,
Leila Adlam, Mark
Swallow coavetx@medistrava.com