Biomarker cohort for delpacibart braxlosiran
(del-brax), the first potential therapy to target DUX4, is
measuring changes in DUX4 regulated biomarkers; del-brax 2 mg/kg
will be administered every six weeks
Enrollment in the del-brax biomarker cohort
expected to be completed in 1H 2025; on track to initiate del-brax
functional cohort in 1H 2025
In previously reported initial data, del-brax
2 mg/kg every six weeks showed unprecedented and consistent
reductions of DUX4 regulated genes, significant decreases in novel
circulating biomarker and creatine kinase, and trends of functional
improvement at the four-month timepoint
SAN
DIEGO, Oct. 30, 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 the
initiation of a biomarker cohort in the Phase 1/2 FORTITUDE™
trial of delpacibart braxlosiran (del-brax/AOC 1020) in people
living with facioscapulohumeral muscular dystrophy (FSHD). Avidity
is pursuing a potential accelerated approval path for del-brax and
expects enrollment in the biomarker cohort to be completed in the
first half of 2025. Avidity also remains on track to initiate a
functional cohort in the first half of 2025. In addition,
enrollment of the FORTITUDE Open-label Extension study (OLE) is
ongoing.
Del-brax is the first investigational therapy designed to treat
the underlying cause of FSHD by directly targeting the
disease-causing gene, double homeobox 4 (DUX4). Currently, there
are no approved therapies for the treatment of FSHD, a rare,
hereditary disorder marked by life-long, relentless loss of muscle
function, significant pain, fatigue, and progressive
disability.
"The initiation of the biomarker cohort marks a key step in our
strategy to pursue a potential accelerated approval path
for del-brax, the first potential treatment to directly target
the root cause of FSHD," said Steve
Hughes, M.D., chief medical officer at Avidity. "We are very
pleased with the del-brax 2 mg/kg data which showed unprecedented
and consistent reductions of DUX4-regulated genes, significant
decreases in novel circulating biomarker and creatine kinase, and
trends of functional improvement with favorable safety and
tolerability at the four-month timepoint. We are advancing our
clinical studies for del-brax as quickly as possible as we
understand the urgency to bring a potential new treatment to people
living with FSHD who have no treatment options."
The biomarker cohort in the FORTITUDE trial will assess the
impact of del-brax 2 mg/kg every six weeks in people living with
FSHD, ages 16-70. The primary endpoints of the study are changes in
DUX4 regulated gene expression and DUX4 regulated circulating
biomarker.
For people living with FSHD it is important to maintain
suppression of DUX4 at all times as aberrant gene expression is
toxic to the muscles. Favorable safety and tolerability, as well as
decreases in circulating biomarker and creatine kinase levels
were similar for patients treated with 2mg/kg or 4mg/kg of
del-brax. Due to this similarity, Avidity selected 2 mg/kg of
del-brax to be administered every six weeks, designed to ensure
continuous suppression of DUX4 for the biomarker and functional
cohorts.
In June of this year, Avidity reported positive initial del-brax
2 mg/kg data at four months from the Phase 1/2 FORTITUDE trial
demonstrating unprecedented and consistent reductions of greater
than 50% in DUX4 regulated genes, mean reductions of 25% or greater
in novel circulating biomarker and creatine kinase, trends of
functional improvement, and favorable safety and tolerability in
people living with FSHD at the 31st Annual FSHD Society
International Research Congress.
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 100 participants with
facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE will
evaluate the safety, tolerability, pharmacokinetics, and
pharmacodynamics of del-brax administered intravenously.
Activity of del-brax will be assessed using key biomarkers,
including DUX4-regulated muscle and circulating biomarkers and
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
FORTITUDE-OLE, an open-label extension study once participation in
the FORTITUDE study is complete. For more information about the
FORTITUDE trial, visit the FORTITUDE study website or
visit http://www.clinicaltrials.gov and search for
NCT05747924.
About the Phase 2 FORTITUDE-OLE™
trial
FORTITUDE-OLE™ is an open-label, multi-center
trial designed to evaluate the long-term safety and tolerability of
delpacibart braxlosiran or del-brax (AOC 1020) in
participants with facioscapulohumeral muscular dystrophy (FSHD) who
were previously enrolled in the FORTITUDE Phase 1/2 trial. This
trial will continue to evaluate the safety, tolerability, PK, PD,
and efficacy of del-brax in participants that enrolled in the
randomized, placebo-controlled, Phase 1/2 FORTITUDE clinical trial.
Participants who enroll in the FORTITUDE-OLE study will receive
del-brax regardless of whether they received active treatment or
placebo in the FORTITUDE study. The total duration of active
treatment with del-brax in the FORTITUDE-OLE is approximately 24
months. Avidity may extend active treatment beyond 24 months at a
future timepoint. For more information on the FORTITUDE-OLE study
click here or visit http://www.clinicaltrials.gov and search for
NCT06547216.
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. Avidity reported positive initial del-brax 2 mg/kg data
at four months 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 FSHD.
Del-brax is currently in Phase 1/2 development as part of the
FORTITUDE™ trial in individuals 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 life-long, relentless loss of muscle function,
significant pain, fatigue, and progressive 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 primary endpoints, design,
goals and other details related to the FORTITUDE™ trial and each of
its cohorts; the status and clinical development of
del-brax, including any potential accelerated approval;
Avidity's plans for the FORTITUDE-OLE™ study and the timing
thereof; 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 a functional cohort
for the FORTITUDE trial and the biomarker and functional cohorts
potentially serving as the basis for registration; 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.
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 clinical holds which may not be timely lifted, recalls or
product liability claims; Avidity's current and planned 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:
Michael MacLean
(619) 837-5014
investors@aviditybio.com
Media Contact:
Navjot Rai
(619) 837-5016
media@aviditybio.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/avidity-biosciences-pursues-potential-accelerated-approval-path-with-initiation-of-biomarker-cohort-in-fortitude-trial-for-delpacibart-braxlosiran-del-braxaoc-1020-in-people-living-with-facioscapulohumeral-muscular-dystrophy-302290828.html
SOURCE Avidity Biosciences, Inc.