Adverum Biotechnologies Provides Program Updates
November 01 2018 - 4:15PM
Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene
therapy company targeting unmet medical needs in ophthalmology and
rare diseases, today provided a program update for its gene therapy
product candidates.
The Company announced its decision to discontinue the
development of ADVM-043, an investigational AAVrh.10-based gene
therapy for the treatment of A1AT deficiency. Based on the review
of the ADVANCE Phase 1/2 study, the data did not demonstrate the
potential to reach M-protein threshold levels of 11µM.
“Over the past year, our team has been focused on the clinical,
regulatory, and manufacturing execution for our lead gene
therapies,” said Leone Patterson, chief executive officer of
Adverum Biotechnologies. “We have carefully evaluated the
preliminary data from the ADVANCE study. While ADVM-043 was safely
administered and was well tolerated, the preliminary protein
expression unfortunately did not reach a level that justified
moving the program forward with the current vector. We truly
appreciate the participation by the investigators, the patients and
their caregivers, the support of the Alpha-1 Foundation and the
dedication of the Adverum team to advance a new treatment option
for patients living with A1AT deficiency. The next steps will be to
conduct additional preclinical studies, utilizing our gene therapy
expertise and platform technology, to determine the best candidates
to advance forward in development for the rare disease programs. An
update on the plan for these programs will be provided in the first
half of 2019.
Ms. Patterson continued, “For wet AMD, we presented long-term
preclinical data this year, at both the ASGCT and ESGCT Annual
Congresses, demonstrating ADVM-022’s durability of biological
activity for 13 months and aflibercept expression up to 22 months
in non-human primates. We remain on-track this quarter to initiate
the OPTIC Phase 1 clinical trial for ADVM-022 in patients with wet
AMD to assess this unique anti-VEGF gene therapy approach using a
single intravitreal administration.”
ADVM-043 for Alpha-1 Antitrypsin (A1AT)
Deficiency in the ADVANCE Phase 1/2 StudyAdverum is
reporting preliminary topline data from the ADVANCE Phase 1/2 study
for ADVM-043 in patients with A1AT deficiency which include data
from the first three cohorts of patients. A total of six patients
have been administered ADVM-043 gene therapy at three increasing
doses (2 subjects per dose). All patients received a prophylactic
tapering corticosteroid regimen. The primary endpoint in the study
is safety and tolerability and secondary endpoints include changes
in plasma concentrations of M-specific A1AT protein. In the study,
patients received a single intravenous administration of ADVM-043,
which utilizes the serotype AAVrh.10 vector expressing A1AT.
Primary Endpoint: Preliminary data demonstrated
that ADVM-043 can be safely administered and is well tolerated with
a mean follow up period of 25 weeks post administration at doses of
1.0 x 1012 vg/kg (8.0 x 1013 vg), 5.0 x 10 12 vg/kg (4.0 x
1014 vg) and 1.5 x 10 13 vg/kg (1.2 x 1015 vg)
respectively. Safety monitoring will be ongoing for up to 52 weeks
post-dosing for all three cohorts.
As of October 24, 2018:
- A total of 15 adverse events (AEs) were reported-- Two AEs of
elevated alanine aminotransferase (ALT; Grade 1, mild) were deemed
possibly related to ADVM-043. The ALTs normalized within a few days
after an increase in prednisone dose
- All AEs were mild (Grade 1) in severity, except for one
unrelated serious adverse event (SAE), considered Grade 3 in
severity attributable to the patient’s preexisting indwelling
port
Secondary Endpoint: Preliminary protein level
data from the study showed, with a mean follow up of 25 weeks post
administration:
- M-specific A1AT protein measurements did not reach clinically
meaningful levels of expression. Although some level of activity
was observed, the protein level only reached a maximum of 200nM in
the study;
- No dose response was observed between the three cohorts
ADVM-022 in Wet Age-related Macular Degeneration
(wAMD)Adverum recently presented long-term preclinical
efficacy data in wAMD, for ADVM-022 a novel gene therapy candidate
utilizing a proprietary vector capsid (AAV.7m8), at the European
Society of Gene & Cell Therapy’s (ESGCT) 26th Annual Congress.
The ADVM-022 data was selected as one of the top-scoring abstracts
and was presented in a lightning talk followed by a poster session
on October 17, 2018. Key highlights included:
- A single intravitreal administration of ADVM-022 in NHPs at
dose ranges of 2 x 10 11 vg/eye to 2 x 10 12 vg/eye provided stable
intraocular expression of aflibercept at levels comparable with the
levels measured in aflibercept recombinant protein-injected eyes
approximately 3 to 4 weeks post-dose in all of the following:
vitreous humor, aqueous humor, retina and choroid
- A single intravitreal administration of ADVM-022 provided
robust expression of aflibercept, sustained for approximately two
years post-dose in non-human primates (NHPs)
In May 2018, long-term preclinical efficacy data in NHP models
on ADVM-022 in wAMD were presented at the American Society of Gene
& Cell Therapy (ASGCT) 21st Annual Meeting. Key highlights
included:
- The efficacy of ADVM-022 at 13 months post-administration was
consistent with earlier reported data, demonstrating that single
intravitreal injection of ADVM-022 was found to be safe and
statistically significant (p<0.0001) in preventing the
development of Grade IV lesions compared to the untreated vehicle
control group
- ADVM-022 induced long-term efficacy that was comparable to
aflibercept, an anti- VEGF standard-of-care therapy. ADVM-022 was
well-tolerated, with no serious adverse events
In September 2018, Adverum received Fast Track designation for
ADVM-022 in wAMD from the U.S. Food and Drug Administration (FDA).
Adverum plans to initiate the OPTIC Phase 1 clinical trial for
ADVM-022 in patients with wAMD in the fourth quarter of 2018.
Rare Disease ProgramsBased on the
most recent data from the ADVANCE clinical trial, the Company is
reviewing the learnings from the study, notably on the AAVrh.10
capsid in order to inform further development of gene therapy
candidates for the treatment of rare diseases. The Company plans to
conduct additional preclinical studies to determine the best gene
therapy candidate to advance. The Company plans to provide an
update on the rare disease programs in the first half of 2019 and
will not submit an IND application for ADVM-053 for the treatment
of hereditary angioedema (HAE) in the fourth quarter of 2018.
About Adverum Biotechnologies,
Inc.Adverum is a clinical-stage gene therapy company
targeting unmet medical needs in ophthalmology and rare diseases.
Leveraging a next-generation adeno-associated virus (AAV)-based
directed evolution platform, Adverum generates product candidates
designed to provide durable efficacy by inducing sustained
expression of a therapeutic protein. Adverum has collaboration
agreements with Regeneron Pharmaceuticals to research, develop, and
commercialize gene therapy products for ophthalmic diseases and
Editas Medicine to explore the delivery of genome editing medicines
for the treatment of inherited retinal diseases. Adverum’s core
capabilities include clinical development and in-house
manufacturing expertise, specifically in process development and
assay development. 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 Adverum’s projected timing to advance
ADVM-022 into the clinic in the fourth quarter, Adverum’s
expectation of providing an update on its rare disease programs in
the first half of 2019, and Adverum’s plans to conduct additional
preclinical studies, all of which are based on certain assumptions
made by Adverum on current conditions, expected future developments
and other factors Adverum believes are appropriate in the
circumstances. Adverum may not consummate any plans or product or
clinical development goals in a timely manner, or at all, or
otherwise be able to carry out the intentions or meet the
expectations or projections disclosed in its forward-looking
statements, and you should not place undue reliance on these
forward-looking statements. Actual results and the timing of events
could differ materially from those anticipated in such
forward-looking statements as a result of various risks and
uncertainties, which include, without limitation, the risk of a
delay in the enrollment of patients in Adverum’s clinical studies
or in the manufacturing of products to be used in such clinical
studies, as well as the risks and uncertainties facing Adverum
described more fully in Adverum’s periodic reports filed with the
Securities and Exchange Commission (SEC), especially under the
caption “Risk Factors” in its latest Quarterly Report on Form 10-Q
filed with the SEC on August 8, 2018. 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.
Investor and Media Inquiries:
Katherine Bock
Vice President Investor Relations & Corporate Communications
Adverum Biotechnologies, Inc.
650-656-9347
kbock@adverum.com
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