Avidity accelerates global Phase 3
HARBOR™ study initiation to Q2 2024 following regulatory
agreement on study design; primary endpoint is video hand opening
time (vHOT) and secondary endpoints include muscle strength and
activities of daily living
Delpacibart etedesiran (AOC 1001) demonstrated
consistent and durable improvements in myotonia, muscle strength
and activities of daily living in people with DM1 in long-term data
from MARINA-OLE™
Delpacibart etedesiran (AOC 1001) data from
MARINA-OLE showed reversal of disease progression in multiple
functional measures in people living with DM1 compared to END-DM1
natural history data
Avidity to host Volume 8 of investor and
analyst event series via webcast March 4,
2024, at 8:00 a.m. ET
SAN
DIEGO, March 4, 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 new
positive long-term AOC 1001 data from the MARINA open-label
extension (MARINA-OLE™) trial showing reversal of
disease progression in people living with myotonic dystrophy type 1
(DM1) across multiple endpoints including vHOT, muscle strength and
activities of daily living when compared to END-DM1 natural history
data. These endpoints are the same key endpoints that will be used
in the global Phase 3 HARBOR™ trial for people
living with DM1. The primary endpoint in the Phase 3 HARBOR trial
is video hand opening time (vHOT), and key secondary endpoints
include muscle strength as measured by hand grip strength and
quantitative muscle testing (QMT) total score, and activities of
daily living as measured by DM1-Activ. Avidity is accelerating the
global Phase 3 HARBOR trial initiation to the second quarter of
2024.
Avidity also announced delpacibart etedesiran as the
approved international nonproprietary name of AOC 1001, abbreviated
as del-desiran. Del-desiran (AOC 1001) is an
investigational treatment designed to address the root cause of
DM1, an underrecognized, progressive and often fatal neuromuscular
disease with no approved therapies.
"The long-term data from the MARINA-OLE study demonstrating that
del-desiran improved measures of disease progression in DM1
patients compared to natural history data is remarkable," said John
W. Day, MD, PhD, Professor of Neurology and Pediatrics, and
Director, Division of Neuromuscular Medicine, Stanford University School of Medicine, an
investigator of the MARINA® and MARINA-OLE trials.
"The favorable long-term safety data and consistent, durable
improvement in myotonia, muscle strength and patient-reported
outcomes measures show the potential of del-desiran to make
a meaningful difference in the lives of DM1 patients. I am very
encouraged by the prospect of del-desiran as a potential
treatment for DM1."
"Initiating our global pivotal study for del-desiran in
the coming months is a significant step forward in bringing a
much-needed treatment to people living with DM1 as quickly as
possible. We are pleased that the agreed upon functional endpoints
in the Phase 3 HARBOR study are the same endpoints in which
del-desiran has demonstrated consistent and durable
improvements in the MARINA studies," said Sarah Boyce, president and chief executive
officer at Avidity. "Thank you to the DM1 community, in particular
- the participants, their families, the investigators and their
teams - for their support, dedication and commitment to the MARINA
program. The depth and breadth of del-desiran data that we
have gathered from these studies offer hope for people living with
DM1, a devastating rare disease for which there are no treatment
options available."
Data Presented at 2024 Muscular Dystrophy Association (MDA)
Clinical & Scientific Conference, March
3-6
MARINA-OLE™ is an open-label, multi-center trial to evaluate
the safety, tolerability, PK, PD, and efficacy of
del-desiran (AOC 1001) in participants that were enrolled in
the randomized, placebo-controlled, Phase 1/2 MARINA®
clinical trial. Participants enrolled in the MARINA-OLE study
receive quarterly doses of del-desiran (AOC 1001) regardless
of whether they received active treatment or placebo in the MARINA
study. All 37 participants that completed the MARINA trial remain
on del-desiran (AOC 1001) in the MARINA-OLE trial.
Long-term efficacy data presented were assessed from 12
participants on 4 mg/kg del-desiran (AOC 1001) in the
MARINA-OLE study. The endpoints used in the MARINA-OLE measure
important aspects of the disease and correspond to those utilized
in the ongoing END-DM1 natural history study.
The long-term data from the MARINA-OLE trial are being presented
in a poster session at the 2024 Muscular Dystrophy Association
(MDA) Clinical & Scientific Conference being held March 3-6, 2024, in Orlando, Florida and can also be found on
Avidity's website on the Publications page.
MARINA-OLE data compared to END-DM1 natural history data
For the first time new data were reported from END-DM1, a natural
history study to establish biomarkers and clinical endpoints in DM1
by understanding the progression of myotonic
dystrophy. Long-term del-desiran (AOC 1001) data from
the MARINA-OLE study show reversal of disease progression in people
living with DM1 across multiple endpoints including myotonia,
muscle strength and patient reported activities of daily living
compared to a matched END-DM1 natural
history study population over one year.
Avidity is grateful to the END-DM1 team for their partnership
over the years and for their approval and permission to share this
analysis from the study.
Del-desiran long-term efficacy data from
MARINA-OLE
In the MARINA-OLE study, del-desiran (AOC 1001) 4 mg/kg
provided consistent and durable improvements in the following:
- Myotonia (video hand opening time, or vHOT)
- Multiple measures of strength:
- Hand grip
- Quantitative Muscle Testing (QMT) total score which includes
hand grip; elbow extension and elbow flexion; knee extension and
knee flexion, and ankle dorsiflexion
- DM1-Activ, a patient reported outcome (PRO) that measures
activities of daily living (e.g., taking a shower, visiting family
or friends, and walking up stairs)
Del-desiran safety and tolerability data from
MARINA-OLE
With over 265 infusions totaling 61.1 patient-years of exposure,
del-desiran (AOC 1001) continues to demonstrate favorable
safety and tolerability. In the MARINA-OLE study of
del-desiran (AOC 1001):
- All related adverse events (AE) were mild or moderate
- The most common related AEs reported in 2 or more participants
in the MARINA-OLE were nausea and headache
- There were no study drug related SAEs
- There have been no discontinuations in the MARINA-OLE
study
Video Webcast Information
The company is hosting
Volume 8 of its investor and analyst event series on March 4, 2024, beginning at 8:00 a.m. ET to discuss new positive long-term
del-desiran (AOC 1001) data from the MARINA-OLE™ trial in
people living with DM1. 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.
About the Phase 1/2
MARINA® Trial
The MARINA® trial was a randomized, double-blind,
placebo-controlled, Phase 1/2 clinical trial that enrolled 38
adults with DM1. The primary objective of this study was to
evaluate the safety and tolerability of single and multiple
ascending doses of del-desiran (AOC 1001) administered
intravenously. The MARINA trial assessed the activity of
del-desiran (AOC 1001) across key biomarkers, including
spliceopathy, an important biomarker for DM1, and knockdown of DMPK
mRNA. Though the Phase 1/2 trial was not powered to assess
functional benefit, it explored the clinical activity of
del-desiran (AOC 1001) in multiple measures of muscle
function including myotonia, muscle strength, measures of mobility
as well as patient reported outcomes and quality of life measures.
Patients had the option to enroll in MARINA-OLE™, an open-label
extension study, at the end of the post-treatment period. For more
information on this study click here or
visit http://www.clinicaltrials.gov and search for
NCT05027269.
About the Phase 2 MARINA-OLE™ Study
MARINA-OLE™ is an open-label, multi-center trial designed to
evaluate the long-term safety and tolerability of
del-desiran (AOC 1001) in participants with DM1 who were
previously enrolled in the MARINA® Phase 1/2 trial. This
trial will continue to evaluate the safety, tolerability, PK, PD,
and efficacy of del-desiran (AOC 1001) in participants
enrolled in the randomized, placebo-controlled, Phase 1/2 MARINA
clinical trial. Participants enrolled in the MARINA-OLE study
receive quarterly doses of del-desiran (AOC 1001) regardless
of whether they received active treatment or placebo in the MARINA
study. The total duration of active treatment with
del-desiran (AOC 1001) in the MARINA-OLE study is
approximately 24 months. Once patients have completed active
treatment, there will be a nine-month safety follow-up period.
Avidity may extend active treatment beyond 24 months at a future
timepoint. For more information on this study
click here or
visit http://www.clinicaltrials.gov and search for
NCT05479981.
About Del-desiran (AOC 1001)
Del-desiran (AOC 1001), Avidity's lead product candidate
utilizing its AOC platform, is designed to address the root cause
of DM1 by reducing levels of a disease-related mRNA called DMPK.
Del-desiran (AOC 1001) consists of a proprietary
monoclonal antibody that binds to the transferrin receptor 1 (TfR1)
conjugated with a siRNA targeting DMPK mRNA. In preclinical
studies, del-desiran (AOC 1001) successfully delivered
siRNAs to muscle cells, resulting in durable, dose-dependent
reductions of DMPK RNA across a broad range of muscles including
skeletal, cardiac, and smooth muscles. Del-desiran (AOC
1001) is currently in Phase 1/2 development with the completed
MARINA® trial and the ongoing MARINA-OLE™ trial in
adults with DM1. The U.S. Food and Drug Administration (FDA) and
European Medicines Agency (EMA) have granted Orphan Designation for
del-desiran (AOC 1001) and the FDA has granted
del-desiran (AOC 1001) Fast Track Designation.
About Myotonic Dystrophy Type 1
Myotonic dystrophy
type 1 (DM1) is an underrecognized, progressive and often fatal
disease caused by a triplet-repeat in the DMPK gene, resulting in a
toxic gain of function mRNA. The disease is highly variable with
respect to severity, presentation and age of onset, however all
forms of DM1 are associated with high levels of disease burden and
may cause premature mortality. DM1 primarily affects skeletal and
cardiac muscle, however patients can suffer from a constellation of
manifestations including myotonia and muscle weakness, respiratory
problems, fatigue, hypersomnia, cardiac abnormalities, severe
gastrointestinal complications, and cognitive and behavioral
impairment. Currently, there are no approved treatments for people
living with DM1.
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 (formerly Twitter).
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 long-term efficacy data associated with
delpacibart etedesiran (del-desiran, or AOC 1001) from the
MARINA-OLE™ study; the impact of such data on the advancement of
del-desiran; a global pivotal Phase 3 trial for
del-desiran, the timing of its initiation and key endpoints
to be used therein; regulatory agreement regarding a Phase 3 trial
for del-desiran; expectations related to the MARINA-OLE
study and del-desiran; timelines for active treatment and
safety follow-up in MARINA-OLE; data from the END-DM1 study and its
importance to the assessment of del-desiran; the potential
of Avidity's product candidates to treat rare diseases and
Avidity's efforts to bring them to people suffering from applicable
diseases; the potential of AOCs to target a range of different
cells and tissues beyond the liver, and to treat cardiac and
immunological diseases; and Avidity's plans to expand its AOC
platform and to invest in its pipeline programs. 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, including, without limitation: Avidity may not
be able to resolve the partial clinical hold related to the serious
adverse event which occurred in the Phase 1/2 MARINA trial, which
may result in delays in the clinical development of
del-desiran; additional participant data related to
del-desiran 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 date
hereof; 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 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.