Avidity plans to accelerate the initiation of
registrational cohorts in FORTITUDE™ trial
Delpacibart braxlosiran (AOC 1020), the first
investigational therapy to target the underlying cause of FSHD,
provided greater than 50% mean reduction across multiple DUX4
regulated gene panels (2 mg/kg at four months)
Trends of functional improvement including
muscle strength, reachable workspace, and positive trends in
patient and clinician reported outcomes demonstrated in people
treated with delpacibart braxlosiran 2 mg/kg at four months
Delpacibart braxlosiran data
demonstrate favorable safety and tolerability with all adverse
events mild or moderate
Volume 9 of virtual investor and analyst
series today, Wednesday, June 12 at 8:00 a.m. ET
SAN DIEGO, June 12, 2024 /PRNewswire/ -- Avidity
Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company
committed to delivering a new class of RNA therapeutics called
Antibody Oligonucleotide Conjugates (AOCs™), today
announced positive initial AOC 1020 data from the Phase 1/2
FORTITUDE™ trial demonstrating unprecedented and
consistent reductions of greater than 50% in DUX4 regulated genes,
trends of functional improvement, and favorable safety and
tolerability in people living with facioscapulohumeral muscular
dystrophy (FSHD). Avidity plans to accelerate initiation of
registrational cohorts in the FORTITUDE™ study.
Avidity also announced delpacibart braxlosiran as the
approved international nonproprietary name of AOC 1020, abbreviated
as del-brax.
Del-brax is the first investigational therapy
designed to treat the underlying cause of FSHD, which is caused by
the abnormal expression of a gene called double homeobox 4 or DUX4.
FSHD is a rare, hereditary disorder marked by life-long, relentless
loss of muscle function, significant pain, fatigue, and progressive
disability. Currently, there are no approved therapies for the
treatment of FSHD.
"As the first therapy to directly target DUX4, it is very
encouraging to see that the del-brax data demonstrate
consistent reductions in DUX4 regulated genes and provided trends
of functional improvement in patients with FSHD at the four-month
timepoint. These early data would support the notion that
del-brax has the potential to change the course of disease
for people living with FSHD," said Jeffrey
M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and
FORTITUDE™ trial investigator. "Early data showing
trends in del-brax to improve muscle strength and function
are very encouraging for patients with FSHD who are in need of
treatments to prevent the muscle weakness and disability that is
associated with this relentlessly, progressive disease."
The AOC 1020 initial data will be highlighted in an oral
presentation at the 31st Annual FSHD Society International Research
Congress, being held June 13-14,
2024, in Denver,
Colorado.
"With the unprecedented del-brax data from the FORTITUDE
trial, we are now focused on accelerating our registrational plans
as we understand the urgency to develop a treatment for people
living with FSHD who have no treatment options," said Sarah Boyce, president and chief executive
officer at Avidity. "By directly targeting the root cause of FSHD,
we believe that del-brax has the potential to be a
first-in-class, best-in-class therapy for people living with FSHD.
This is our third rare muscle disease program to show delivery to
muscle and target engagement and second therapy to provide signs of
functional improvement in patients with rare neuromuscular
diseases, further reinforcing the promise of our AOC platform to
profoundly improve people's lives by revolutionizing the delivery
of RNA therapeutics."
The initial assessment from the randomized, double-blind,
placebo-controlled Phase 1/2 FORTITUDE trial of del-brax
provides a four-month look at the safety and tolerability for all
39 participants across two dose levels (2 mg/kg and 4 mg/kg). For
the four-month assessment in the 2 mg/kg cohort, participants
received a single-dose of 1 mg/kg del-brax followed by two
doses of 2 mg/kg del-brax (siRNA dose), or placebo. Data on
DUX4 regulated genes, circulating biomarkers and muscle strength
and function were assessed from 12 participants in the 2 mg/kg
cohort.
In the Phase 1/2 FORTITUDE study, del-brax
demonstrated:
- Greater than 50% mean reductions in DUX4 regulated genes across
multiple panels for DUX4 regulated gene expression in muscle
- All participants treated with del-brax showed reductions
greater than 20% in DUX4 regulated genes
- Mean reductions of 25% or greater in novel circulating
biomarker and creatine kinase
- Trends of functional improvements including increased strength
in upper and lower limb muscles, and muscle function as measured by
reachable workspace (RWS) compared to placebo and the ReSolve
natural history study
- Trends of improvement in patient and clinician reported
outcomes
- Favorable safety and tolerability with all adverse events (AEs)
mild or moderate, no serious adverse events and no
discontinuations
"Data from the FORTITUDE trial are very promising for people
living with FSHD as the progression of the disease can make it
increasingly difficult to perform critical day-to-day activities,
pursue work and can affect many aspects of life, including family
and social life," said Mark Stone,
president and chief executive officer of FSHD Society. "FSHD is one
of the most prevalent forms of muscular dystrophy and currently,
there are no treatment options. The initial del-brax data
offers real hope for those living with the disease, their families,
and their caregivers, who are desperately waiting for a
treatment."
Video Webcast Information
The company is hosting
Volume 9 of its investor and analyst event series on June 12,
2024, beginning at 8:00 a.m. ET to discuss the initial
data from the FORTITUDE™ trial of del-brax in
people living with FSHD. The virtual event will be available via a
live video webcast and can be accessed here or from the
"Events and Presentations" page in the "Investors" section of
Avidity's website. A replay of the webcast will be archived on
Avidity's website following the event.
The management team will be joined by Jeffrey M. Statland, M.D., Professor of
Neurology, University of Kansas Medical
Center, and FORTITUDE™ trial investigator. Dr.
Statland is one of the principal investigators in the ReSolve
study, an ongoing natural history study being led by the FSHD
Clinical Trial Research Network (CTRN).
About the Phase 1/2 FORTITUDE™ trial
The FORTITUDE™ trial is a randomized,
placebo-controlled, double-blind, Phase 1/2 clinical trial designed
to evaluate single and multiple doses of delpacibart braxlosiran or
del-brax (AOC 1020) in approximately 39 adult participants
with facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE will
evaluate the safety, tolerability, pharmacokinetics, and
pharmacodynamics of del-brax administered intravenously,
with the primary objective being the safety and tolerability of
del-brax in FSHD patients. Activity of
del-brax will be assessed using key biomarkers,
including magnetic resonance imaging (MRI) measures of muscle
volume and composition. Though the Phase 1/2 trial is not
statistically powered to assess functional benefit, it will explore
the clinical activity of del-brax including measures of
mobility and muscle strength as well as patient reported outcomes
and quality of life measures. Participants will have the option to
enroll in an open-label extension study at the end of the treatment
period in the FORTITUDE study. For more information about the
FORTITUDE trial, visit the FORTITUDE study website or
visit http://www.clinicaltrials.gov and search for
NCT05747924.
About Del-brax (AOC 1020)
Del-brax (AOC 1020) is designed to treat the underlying
cause of FSHD, which is caused by the abnormal expression of a gene
called double homeobox 4 or DUX4. The abnormal expression of DUX4
protein leads to changes in gene expression in muscle cells that
are associated with the life-long, progressive loss of muscle
function in patients with FSHD. Del-brax aims to reduce the
expression of DUX4 mRNA and DUX4 protein in muscles in people with
FSHD. Del-brax consists of a proprietary monoclonal antibody
that binds to the transferrin receptor 1 (TfR1) conjugated with a
siRNA targeting DUX4 mRNA. In preclinical studies, a single
intravenous dose with the murine version of del-brax
prevented development of muscle weakness demonstrated by three
functional assays - treadmill running, in vivo force and compound
muscle action potential. Del-brax is currently in Phase 1/2
development as part of the FORTITUDE™ trial in adults
with FSHD. The U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMA) have granted Orphan designation for
del-brax and the FDA has granted del-brax Fast Track
designation.
About Facioscapulohumeral Muscular Dystrophy
(FSHD)
Facioscapulohumeral muscular dystrophy (FSHD) is a
rare, progressive, and variable hereditary muscle-weakening
condition marked by significant pain, fatigue, and disability. It
is characterized by progressive and often asymmetric skeletal
muscle loss that initially causes weakness in muscles in the face,
shoulders, arms and trunk and progresses to weakness in muscles in
the lower body. FSHD is an autosomal dominant disease caused by the
aberrant expression of the DUX4 (double homeobox 4) gene in the
skeletal muscle, which activates genes that are toxic to muscle
cells and leads to a series of downstream events that result in
skeletal muscle wasting and compromised muscle function. Skeletal
muscle weakness results in physical limitations throughout the
whole body, including an inability to lift arms for more than a few
seconds, loss of ability to show facial expressions and serious
speech impediments. These symptoms cause many people affected by
FSHD to become dependent on the use of a wheelchair for mobility.
Currently, there are no approved treatments for people living with
FSHD.
About Avidity
Avidity Biosciences, Inc.'s mission is to profoundly improve
people's lives by delivering a new class of RNA therapeutics -
Antibody Oligonucleotide Conjugates (AOCs™). Avidity is
revolutionizing the field of RNA with its proprietary AOCs, which
are designed to combine the specificity of monoclonal antibodies
with the precision of oligonucleotide therapies to address targets
and diseases previously unreachable with existing RNA therapies.
Utilizing its proprietary AOC platform, Avidity demonstrated the
first-ever successful targeted delivery of RNA into muscle and is
leading the field with clinical development programs for three rare
muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular
dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD).
Avidity is broadening the reach of AOCs with its advancing and
expanding pipeline including programs in cardiology and immunology
through internal discovery efforts and key partnerships. Avidity is
headquartered in San Diego, CA. For more information
about our AOC platform, clinical development pipeline and people,
please visit www.aviditybiosciences.com and engage with
us on LinkedIn and X.
Forward-Looking Statements
Avidity cautions readers
that statements contained in this press release regarding matters
that are not historical facts are forward-looking statements. These
statements are based on the company's current beliefs and
expectations. Such forward-looking statements include, but are not
limited to, statements regarding: the characterization of safety,
tolerability and functional data associated with del-brax
from the Phase 1/2 FORTITUDE™ trial; the impact of such
data on the advancement of del-brax; the plans and timing of
adding cohorts for the FORTITUDE trial and such cohorts potentially
serving as the basis for registration; the status and potential of
del-brax as a first-in-class, best-in-class treatment for
FSHD; the potential of Avidity's product candidates to treat rare
diseases and Avidity's efforts to bring them to people suffering
from applicable diseases; and the potential of AOCs to target a
range of different cells and tissues beyond the liver, and to treat
cardiac and immunological diseases. This press release also
contains estimates and other statistical data made by independent
parties and by us. This data involves a number of assumptions and
limitations, and the reader is cautioned not to give undue weight
to such estimates.
The inclusion of forward-looking statements should not be
regarded as a representation by Avidity that any of these plans
will be achieved. Actual results may differ from those set forth in
this press release due to the risks and uncertainties inherent in
Avidity's business and those beyond its control, including, without
limitation: preliminary results of a clinical trial are not
necessarily indicative of final results and additional participant
data related to del-brax that continues to become available
may be inconsistent with the data produced as of the date hereof,
and further analysis of existing data and analysis of new data may
lead to conclusions different from those established as of the data
cutoff; unexpected adverse side effects to, or inadequate efficacy
of, Avidity's product candidates that may delay or limit their
development, regulatory approval and/or commercialization, or may
result in additional clinical holds which may not be timely lifted,
recalls or product liability claims; Avidity's planned additional
cohorts in the FORTITUDE trial may not support the
registration of del-brax; Avidity is early in its
development efforts; Avidity's approach to the discovery and
development of product candidates based on its AOC platform is
unproven, and the company does not know whether it will be able to
develop any products of commercial value; potential delays in the
commencement, enrollment, data readouts and completion of
preclinical studies or clinical trials; Avidity's dependence on
third parties in connection with preclinical and clinical testing
and product manufacturing; regulatory developments in the United States and foreign countries; and
other risks described in Avidity's Annual Report on Form 10-K for
the fiscal year ended December 31,
2023, filed with the Securities and Exchange Commission
(SEC) on February 28, 2024, and in
subsequent filings with the SEC. Avidity cautions readers not to
place undue reliance on these forward-looking statements, which
speak only as of the date hereof, and the company undertakes no
obligation to update such statements to reflect events that occur
or circumstances that arise after the date hereof. All
forward-looking statements are qualified in their entirety by this
cautionary statement, which is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of
1995.
Investor Contact:
Geoffrey Grande, CFA
(619) 837-5014
investors@aviditybio.com
Media Contact:
Navjot Rai
(619) 837-5016
media@aviditybio.com
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SOURCE Avidity Biosciences, Inc.