Atsena Therapeutics Announces Positive Clinical Data from the First Cohort of Phase I/II Trial Evaluating ATSN-201 Gene Therapy for the Treatment of X-linked Retinoschisis (XLRS)
01 Mayo 2024 - 6:30AM
Atsena Therapeutics, a clinical-stage gene therapy company focused
on bringing the life-changing power of genetic medicine to reverse
or prevent blindness, today announced positive preliminary data
from the first cohort of the ongoing LIGHTHOUSE study, a Phase I/II
clinical trial evaluating subretinal injection of ATSN-201 for the
treatment of X-linked retinoschisis (XLRS). ATSN-201 utilizes
AAV.SPR, the company’s novel spreading capsid, to achieve
therapeutic levels of gene expression in photoreceptors of the
central retina while avoiding the surgical risks of foveal
detachment.
The LIGHTHOUSE study is evaluating ATSN-201 in male patients
ages 6 and older with a clinical diagnosis of XLRS caused by
mutations in the RS1 gene. XLRS is characterized by schisis, or
abnormal splitting of retinal layers, which causes impaired visual
acuity that is not correctable with glasses and leads to
progressive vision loss and ultimately blindness. XLRS impacts
approximately 30,000 males in the U.S. and EU and there are no
approved treatments.
In the first (low-dose) cohort of the LIGHTHOUSE study, two of
the three patients showed extensive resolution of schisis beginning
at 8 weeks after dosing. Additional and continued resolution of
schisis was observed through week 24, the latest time point
available. Notably, areas of schisis cavity resolution were found
both inside and well outside of the subretinal injection blebs,
indicating that AAV.SPR is spreading laterally from the injection
blebs, consistent with expectations of this novel, laterally
spreading capsid.
Early efficacy was also observed using microperimetry, with
functional improvements seen in the same locations as structural
improvements. Improvements of up to 14 dB were seen in one patient,
with 38 loci showing an improvement of greater than 7 dB. The U.S.
Food and Drug Administration considers an improvement of at least 7
dB at 5 or more prespecified loci to be clinically meaningful.
ATSN-201 was well tolerated in all three XLRS patients in the
first cohort and no serious adverse events were reported. These
results demonstrate, for the first time, the ability to safely
administer subretinal injections in patients with extensive retinal
schisis.
"The favorable safety profile and early efficacy observed in
patients treated with ATSN-201 in the low-dose cohort of the
LIGHTHOUSE study are very encouraging,” said Kenji Fujita, MD,
Chief Medical Officer of Atsena Therapeutics. “We’re particularly
pleased to have clinical validation of AAV.SPR’s ability to spread
laterally well beyond the subretinal injection blebs. With dosing
of patients in the mid-dose cohort underway, we look forward to the
swift progression of this first clinical trial utilizing our novel
spreading capsid and to the continued development of our
best-in-class gene therapy candidate for XLRS patients who
currently lack an approved treatment option.”
Safety data from the first cohort of the LIGHTHOUSE study will
be presented at the Retinal Cell and Gene Therapy Innovation Summit
2024 being held Friday, May 3, 2024, in Seattle. Details are as
follows:
Title: Preliminary safety of ATSN-201 subretinal gene therapy in
patients with X-linked retinoschisisPresenter: Christine Kay, MD,
Clinical Ophthalmology Advisor, Atsena TherapeuticsTime:
11:05-11:20 a.m. PT
For more information about the Phase I/II open-label,
dose-escalation, and dose-expansion clinical trial with four active
study sites, visit ClinicalTrials.gov (Identifier:
NCT05878860).
About X-linked Retinoschisis (XLRS)XLRS is a
monogenic X-linked disease caused by mutations in the RS1 gene
which encodes retinoschisin, a protein secreted primarily by
photoreceptors. RS1 is localized to the extracellular surface of
rods, cones, and bipolar cells. XLRS is characterized by schisis,
or abnormal splitting of retinal layers, which causes impaired
visual acuity that is not correctable with glasses and leads to
progressive vision loss and ultimately blindness. XLRS primarily
affects males and is typically diagnosed in early childhood.
Approximately 30,000 males in the U.S. and EU have XLRS, for which
there are currently no approved treatments.
About AAV.SPRAAV.SPR, one of Atsena’s novel
capsids, spreads laterally beyond the subretinal injection site to
enable safe and efficient transduction of the central retina (where
schisis cavities predominate in XLRS patient retinas) when injected
into areas outside the macula. A preclinical study in non-human
primates demonstrated that AAV.SPR promotes transgene expression
well beyond subretinal injection bleb margins. This is in stark
contrast to benchmark AAV vectors, which remain confined to the
original bleb margins. At clinically relevant doses, AAV.SPR
efficiently transduces foveal cones without the need for surgical
detachment and does not cause inflammation. For more information
about the preclinical study and how AAV.SPR works, visit
https://atsenatx.com/our-approach/laterally-spreading-aav/.
About Atsena TherapeuticsAtsena Therapeutics is
a clinical-stage gene therapy company developing best-in-class
treatments for the reversal or prevention of blindness from
inherited retinal diseases. The company’s lead program is
evaluating ATSN-201 in an ongoing Phase I/II clinical trial for
X-linked retinoschisis (XLRS), a progressive genetic condition
affecting boys and men that is typically diagnosed in childhood.
Another ongoing Phase I/II clinical trial is evaluating ATSN-101
for Leber congenital amaurosis type 1 (LCA1), one of the most
common causes of blindness in children. Atsena’s pipeline is
powered by novel adeno-associated virus (AAV) technology tailored
to overcome the hurdles presented by inherited retinal diseases.
Founded by pioneers in ocular gene therapy, Atsena is led by an
experienced team dedicated to addressing the needs of patients with
vision loss. For more information, please visit
https://atsenatx.com/.
Media Contact:Tony Plohoros6 Degrees(908)
591-2839tplohoros@6degreespr.com
Business Contact:info@atsenatx.com