Adverum Biotechnologies Announces Positive Aflibercept Protein Level Data from the LUNA Phase 2 Trial
26 Septiembre 2023 - 3:05PM
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 initial
aflibercept protein expression data from its ongoing Phase 2 LUNA
trial evaluating ixoberogene soroparvovec (Ixo-vec) for the
treatment of wet age-related macular degeneration (wet AMD). New
data announced today include aflibercept protein levels for both
the 2E11 and 6E10 vg/eye doses, suggesting that both doses are
within the therapeutically active range. Notably, these protein
expression levels are consistent with levels observed in the OPTIC
trial, in which aflibercept levels and corresponding clinical
activity have been sustained in patients through multiple years of
follow-up after a single Ixo-vec injection.
“This first data cut from the LUNA trial is highly encouraging,
showing similar aflibercept expression levels at the 2E11 and 6E10
doses,” stated Laurent Fischer, M.D., president and chief executive
officer of Adverum Biotechnologies. “Unlike the current standard of
care that requires multiple bolus injections in the eye every year
to maintain sufficient levels of aflibercept, gene therapy has the
potential to dramatically reduce treatment burden for the life of
the patient by delivering durable therapeutic levels of anti-VEGF.
The aflibercept levels across the 2E11 and 6E10 doses are in the
range observed in the OPTIC trial and in the range that was seen in
previously presented non-human primate data. The efficacy of
Ixo-vec at the 2E11 dose in OPTIC remain very promising. LUNA was
designed to further optimize Ixo-vec's profile, by exploring
improved corticosteroid prophylactic regimens and the potential to
dose lower. Our preliminary LUNA data reinforce our hypothesis that
Ixo-vec at both the 2E11 and 6E10 doses has the potential to
produce a robust clinical activity with an acceptable safety
profile.”
Dr. Fischer continued, “We are pleased with the promising
emerging LUNA clinical activity and safety data. At AAO this year,
we look forward to presenting updated long-term follow-up data from
the OPTIC trial, showing aflibercept protein levels out to four
years, and clinical efficacy and safety data out to three years
after a single Ixo-vec injection. We also look forward to providing
initial LUNA clinical activity and safety data once a meaningful
subset of patients have completed the corticosteroid prophylactic
taper regimens.”
“The preliminary aqueous aflibercept protein data are consistent
with levels known to be therapeutic and suggest that, in
previously-treated neovascular age-related macular degeneration
patients, both the 2E11 and 6E10 doses of Ixo-vec have the
potential for sustained efficacy after a single administration,”
said Arshad M. Khanani, M.D., M.A., managing partner and director
of clinical research, Sierra Eye Associates, member of Adverum’s
Scientific Advisory Board and principal investigator of the LUNA
and the OPTIC trials. “Ixo-vec utilizes the 7m8 capsid developed
via directed evolution to enhance retinal transduction and to
deliver therapy where it is needed most. These results from the
LUNA study could be clinically meaningful as the aflibercept levels
measured in this trial are comparable to the sustained aflibercept
levels seen in patients treated in the OPTIC trial.”
Ixo-vec Phase 2 LUNA Preliminary Aflibercept Protein
Level Data Highlights
Background:
- Ixo-vec is an aflibercept-encoding
AAV.7m8 vector designed via directed evolution to cross the inner
limiting membrane, enabling in-clinic IVT delivery and enhanced
retinal transduction.
- Aqueous aflibercept protein levels
in LUNA
- The Phase 2 LUNA trial was designed
to inform the selection of Ixo-vec dose(s) and corticosteroid
prophylactic regimen(s) for the design of Phase 3 registrational
trials.
- Aqueous aflibercept levels measured
in LUNA at this early week 14 time point are a predictive biomarker
of the higher and therapeutically relevant aflibercept levels in
the retina and choroid.
- Non-human primate data confirm
robust expression of aflibercept in the retina and choroid after a
single IVT injection of Ixo-vec at levels approximately nine-fold
higher than those measured in the aqueous humor.
- OPTIC clinical activity and safety
- In OPTIC, the 2E11 dose of Ixo-vec
performed well through two years, demonstrating efficacy that
remains highly promising, with an acceptable safety profile.
- Patients demonstrated early
aflibercept levels sustained through at least three years of
follow-up and also demonstrated clinical benefit, including vision
maintenance, fluid control and a significant reduction in treatment
burden.
- OPTIC patients with a broad range of
aqueous aflibercept levels achieved clinical benefit. Notably one
subject had an 85% reduction in annualized supplemental aflibercept
injections over 45 months of follow up and had aflibercept levels
at multiple time points below or at the threshold of the limit of
quantification of our assay (data on file).
Trial Design & Key Baseline Characteristics:
- The LUNA trial is evaluating the
efficacy and safety of Ixo-vec in 60 subjects randomized equally
between the 2E11 and 6E10 doses.
- LUNA was fully enrolled in August
2023, and as of the July 24, 2023 data cut-off, 12 patient samples
have been collected and analyzed for aflibercept protein levels in
the aqueous humor.
- The LUNA trial population has
similar visual acuity and injection frequency baseline
characteristics to the study population of OPTIC.
- In particular, the mean annualized
anti-VEGF injection rate in the 12 months prior to Ixo-vec
treatment in LUNA is approximately nine injections, indicating that
these subjects require frequent injections, administered
approximately every six weeks.
Aqueous Aflibercept Protein Expression Levels:
- Aflibercept protein data suggest
Ixo-vec at the 2E11 and 6E10 doses deliver similar levels of
aflibercept that are both within the therapeutically active range
based on OPTIC and non-human primate data.
*In LUNA, 12 of 14 eligible subjects had aqueous taps as of the
July 24, 2023 data cut-off date. Data are shown for nine LUNA
subjects. The other three subjects (including subjects at both dose
levels) had aflibercept levels below the limit of quantification
(25ng/ml) of our ELISA assay.
Preliminary LUNA Clinical Activity and Safety Summary:
- Ixo-vec early clinical activity is
encouraging and as anticipated, Ixo-vec has been generally
well-tolerated with a favorable safety profile as of the data
cut-off date.
- Over 90% of subjects were still
receiving corticosteroid prophylactic taper as of the data cut-off
date.
Anticipated Clinical Program Milestones
Q4 2023: |
Presentation of OPTIC four-year Ixo-vec aflibercept protein
expression data and three-year extension efficacy and safety data
at the American Academy Ophthalmology (AAO) Meeting in November
2023. |
|
|
Q4 2023: |
LUNA preliminary efficacy and
safety data. |
|
|
Mid-2024: |
Additional LUNA data, including
the 26-week interim analysis. |
|
|
About Wet Age-Related Macular DegenerationWet
AMD, also known as neovascular AMD or nAMD, is a VEGF driven
advanced form of AMD affecting approximately 10% of patients living
with AMD associated with the build-up of fluid in the macula and
the retina. 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. The current
standard of care requires frequent life-long repeated bolus
injections of anti-VEGF in the eye. IVT gene therapy has the
promise to preserve vision and reduce most or all injections for
the life of the patient by delivering stable therapeutic levels of
anti-VEGF to control macular fluid.
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 has 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 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. Additionally,
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, anticipated preliminary and
interim data from the LUNA trial and pipeline programs. 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 June 30, 2023 filed with the SEC on August 10, 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,
except as required by law.
Inquiries: Adverum Investor RelationsEmail:
ir@adverum.com
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/9317bf70-25b3-4a58-ae91-9d5796b4560d
Adverum Biotechnologies (NASDAQ:ADVM)
Gráfica de Acción Histórica
De Abr 2024 a May 2024
Adverum Biotechnologies (NASDAQ:ADVM)
Gráfica de Acción Histórica
De May 2023 a May 2024