Adverum Biotechnologies Presents Nonclinical Data in Support of Ixo-vec’s Phase 2 Clinical Development at ASGCT 2023 Annual Meeting
18 Mayo 2023 - 8:00AM
Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage
company that aims to establish gene therapy as a new standard of
care for highly prevalent ocular diseases, today announced new
nonclinical data supporting the use of ixoberogene soroparvovec
(Ixo-vec, formerly referred to as ADVM-022) at the American Society
of Gene & Cell Therapy (ASGCT) 2023 Annual Meeting in Los
Angeles, California. Ixo-vec is currently being evaluated in the
Phase 2 LUNA trial in wet age-related macular degeneration (wet
AMD). The data being presented at ASGCT are featured in an oral
presentation on the identification of dose-dependent immune
landscape signatures in nonhuman primates (NHPs), an oral
presentation of nonclinical data that supports the potential for
staggered, bilateral dosing of Ixo-vec and a poster presentation
evaluating Ixo-vec per cell vector genome (vg) biodistribution and
mRNA expression in NHPs.
“Our nonclinical data presented at ASGCT support the use of the
human equivalent doses 2x10^11 vg/eye and 6x10^10 vg/eye doses
being evaluated in the LUNA trial,” stated Brigit Riley, Ph.D.,
chief scientific officer at Adverum. “It is well understood that
gene therapy products cause dose-dependent inflammation regardless
of serotype and route of administration. We were
pleased to see that the Ixo-vec doses advanced in the LUNA trial
can achieve therapeutic aflibercept levels in NHPs that improve the
inflammation profile. These data support our
development efforts around lower dose administration of Ixo-vec and
enhanced prophylactic corticosteroid regimens being evaluated in
LUNA. We look forward to sharing interim 14-week aflibercept
protein levels for a percentage of the cohort in the LUNA trial in
the third quarter of this year.”
Data Highlights
- Ixo-vec aflibercept protein levels were consistent across
2x10^11 vg/eye (2E11) and 6x10^10 vg/eye (6E10) doses, suggesting
lower doses may offer similarly robust levels of efficacy with
improved inflammation profiles.
- Immune landscape signatures demonstrated a dose-dependent
activation of innate and adaptive immune response consistent with
AAV-associated inflammation.
- No evidence that harnessing ocular cells as biofactories to
produce aflibercept leads to aflibercept expression-related
toxicity/inflammation.
- No evidence that ciliary body architecture was directly
affected by Ixo-vec.
- In an encore to the company’s recent presentation at the
Association for Research in Vision and Ophthalmology (ARVO) 2023
Annual Meeting, Adverum presented data outlining the rationale for
staggered, bilateral administration of Ixo-vec in patients with
bilateral disease. Up to 42% of wet AMD patients experience
neovascularization in the second eye in the first two to three
years following diagnosis in the primary eye, indicative of an
unmet need for many wet AMD patients globally.
- Ixo-vec was administered to one eye and then two months later
to the fellow eye of NHPs. Following the second, staggered
administration of Ixo-vec, the fellow eye demonstrated aflibercept
protein levels within the targeted therapeutic
range.
- Staggered, bilateral intravitreal (IVT) administration of
Ixo-vec was well tolerated, with encouraging therapeutic activity
as well as no increase in intraocular inflammation levels.
- These data demonstrate for the first time that the ocular
humoral response in NHP is compartmentalized to the eye dosed with
AAV capsid.
- An evaluation of intraocular per cell biodistribution of
Ixo-vec vg and aflibercept mRNA via in-situ hybridization in NHP
eyes at the human equivalent dose of 2E11 and 6E10 revealed:
- Intraocular fluid convection together with anterior and
posterior fluid outflow influence ubiquitous distribution of vgs
from IVT-delivered ocular gene therapy products.
- Ixo-vec drives aflibercept mRNA
expression in anterior and posterior tissues with most prominent
expression in the macula and peripheral retina.
- Localization of aflibercept mRNA
expression in retina is influenced by the internal limiting
membrane (ILM) barrier.
- We are now able to identify on a per
cell basis what ocular cells produce Ixo-vec together with a more
robust picture of vector flow within the eye that informs ongoing
Ixo-vec product development.
The ASGCT poster and oral presentations will be made available
on the Publications page of the Adverum website.
About Wet Age-Related Macular DegenerationWet
AMD, also known as neovascular AMD or nAMD, is an advanced form of
AMD affecting approximately 10% of patients living with AMD. Wet
AMD is a leading cause of blindness in people over 65 years of age,
with approximately 20 million individuals worldwide living with
this condition. New cases of wet AMD are expected to grow
significantly worldwide as populations age. AMD is expected to
impact 288 million people worldwide by 2040, with wet AMD
accounting for approximately 10% of those cases. Additionally, wet
AMD is a bilateral disease and incidence of nAMD in the second eye
is up to 42% in the first two to three years.
About Ixo-vec in Wet AMDAdverum is
developing ixoberogene soroparvovec (Ixo-vec, formerly
referred to as ADVM-022), its clinical-stage gene therapy product
candidate, for the treatment of wet AMD. Ixo-vec utilizes a
proprietary vector capsid, AAV.7m8, carrying an aflibercept coding
sequence under the control of a proprietary expression cassette.
Unlike other ophthalmic gene therapies that require surgery to
administer the gene therapy under the retina (sub-retinal
approach), Ixo-vec is designed to be administered as a one-time IVT
injection in the physician’s office, deliver long-term efficacy,
reduce the burden of frequent anti-vascular endothelial growth
factor (VEGF) injections, optimize patient compliance and improve
vision outcomes for patients with wet AMD. In recognition of the
need for new treatment options for wet AMD, the U.S. Food and Drug
Administration granted Fast Track designation for Ixo-vec for the
treatment of wet AMD. Ixo-vec also received PRIME designation from
the European Medicines Agency and the Innovation Passport from the
United Kingdom’s Medicines and Healthcare Products Regulatory
Agency for the treatment of wet AMD.
About LUNA Trial of Ixo-vec in Wet AMDThe LUNA
trial is a double-masked, randomized, Phase 2 trial being conducted
at approximately 40 sites in the U.S. and Europe. LUNA will
evaluate Ixo-vec in subjects with wet AMD who are 50 years or older
and have demonstrated a response to anti-VEGF treatment. Up to 72
subjects will be randomized equally between the previously
evaluated 2E11 vg/eye dose and a new, lower 6E10 vg/eye dose. Four
prophylactic corticosteroid regimens will be studied with the aim
of establishing a prophylactic corticosteroid regimen with minimal
need for inflammation management post prophylaxis. Prophylactic
regimens being evaluated include 22 weeks of a tapered regimen of
topical difluprednate (Durezol®), a single administration of IVT
dexamethasone (Ozurdex®), and a combination of either topical
Durezol® or IVT Ozurdex® with up to 10 weeks of a tapered regimen
of oral prednisone. All four prophylactic corticosteroid regimens
in LUNA cover the period of peak immunogenicity observed in
non-clinical studies and in the Phase 1 OPTIC study.
The LUNA trial primary endpoints are mean change in best
corrected visual acuity (BCVA) from baseline to one year, as well
as the incidence and severity of adverse events. Important
secondary endpoints in LUNA include the mean change in central
subfield thickness (CST) from baseline to one year and assessing
the effectiveness of prophylactic corticosteroid regimens on
minimizing inflammation. Additionally, LUNA will assess aflibercept
protein levels starting at Week 14 and include an interim analysis
at Week 26. Study participants will have the option to enroll in a
long-term extension study.
About Adverum BiotechnologiesAdverum
Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that
aims to establish gene therapy as a new standard of care for highly
prevalent ocular diseases with the aspiration of developing
functional cures to restore vision and prevent blindness.
Leveraging the capabilities of its proprietary intravitreal (IVT)
platform, Adverum is developing durable, single-administration
therapies, designed to be delivered in physicians’ offices, to
eliminate the need for frequent ocular injections to treat these
diseases. Adverum is evaluating its novel gene therapy candidate,
ixoberogene soroparvovec (Ixo-vec, formerly referred to as
ADVM-022), as a one-time, IVT injection for patients with
neovascular or wet age-related macular degeneration. By overcoming
the challenges associated with current treatment paradigms for
debilitating ocular diseases, Adverum aspires to transform the
standard of care, preserve vision, and create a profound societal
impact around the globe. For more information, please visit
www.adverum.com.
Forward-looking Statements Statements contained
in this press release regarding events or results that may occur in
the future are “forward-looking statements” within the meaning of
the Private Securities Litigation Reform Act of 1995. Such
statements include but are not limited to statements regarding the
potential benefits of Ixo-vec in the treatment of wet AMD, the
design of and enrollment in the LUNA trial, including the
prophylactic corticosteroid regimens, and anticipated interim data
from the LUNA trial. Actual results could differ materially from
those anticipated in such forward-looking statements as a result of
various risks and uncertainties, including risks inherent to,
without limitation: Adverum’s novel technology, which makes it
difficult to predict the timing of commencement and completion of
clinical trials; regulatory uncertainties; enrollment
uncertainties; the results of early clinical trials not always
being predictive of future clinical trials and results; and the
potential for future complications or side effects in connection
with use of Ixo-vec. Additional risks and uncertainties facing
Adverum are set forth under the caption “Risk Factors” and
elsewhere in Adverum’s Securities and Exchange Commission (SEC)
filings and reports, including Adverum’s Quarterly Report on Form
10-Q for the quarter ended March 31, 2023 filed with the SEC on May
11, 2023. All forward-looking statements contained in this press
release speak only as of the date on which they were made. Adverum
undertakes no obligation to update such statements to reflect
events that occur or circumstances that exist after the date on
which they were made.
Corporate, Investor and Media Inquiries
Anand ReddiVice President, Head of Corporate Strategy, External
Affairs and EngagementAdverum Biotechnologies, Inc.T:
650-649-1358E: areddi@adverum.com
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