New AOC 1001 data demonstrate improvement in
additional functional measures including hand grip, muscle strength
and patient reported outcomes, augmenting previously reported
positive data showing improvements in myotonia, muscle strength and
mobility
New long-term safety data of AOC 1001 continue
to demonstrate favorable safety and tolerability with over 200
infusions totaling 46.2 patient-years of exposure
Data from 12 participants dose-escalated from
2 mg/kg to 4 mg/kg of AOC 1001 as part of the easement of the
partial clinical hold showed no neurological events and no MRI
changes following dosing
Company plans to share AOC 1001 data from
MARINA-OLE study in first half of 2024 and is finalizing Phase 3
study design and global regulatory path for AOC 1001
SAN
DIEGO, Oct. 7, 2023 /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 AOC 1001 data demonstrating improvement in
multiple additional functional endpoints and favorable long-term
safety and tolerability in people living with myotonic dystrophy
type 1 (DM1). AOC 1001, Avidity's lead clinical program utilizing
its AOC platform, is designed to address the root cause of DM1, an
underrecognized, progressive and often fatal neuromuscular disease
with no approved therapies. The AOC 1001 data from the Phase 1/2
MARINA® trial and MARINA open-label extension
(MARINA-OLE™) study will be highlighted in an oral
presentation at the 28th Annual Congress of the World Muscle
Society (WMS) in Charleston, South
Carolina and can be found on Avidity's website on the
Publications page.
"The new AOC 1001 data presented today demonstrating
improvements in muscle strength and patient reported outcomes add
to the previously reported positive topline data showing
improvements in myotonia and mobility. The AOC 1001 data continues
to be quite remarkable with consistent improvements across multiple
functional endpoints," said Nicholas E.
Johnson, M.D., M.Sci., FAAN, associate professor and vice
chair of research in the Department of Neurology at Virginia Commonwealth University, lead investigator
of the MARINA trial and study presenter. "The AOC 1001 functional
data coupled with the long-term favorable tolerability and safety
data provide us with hope that AOC 1001 has the potential to help
patients with DM1, who are in desperate need of treatments."
The new AOC 1001 data demonstrate improvement in additional
functional measures including hand grip, muscle strength and
patient reported outcomes, augmenting previously reported positive
data showing improvements in myotonia, muscle strength and
mobility. With new long-term safety data from over 200 infusions
totaling 46.2 patient-years of exposure, AOC 1001 continues to
demonstrate favorable safety and tolerability with most adverse
events (AEs) mild to moderate.
"Data from MARINA and MARINA-OLE reinforce our belief in the
potential of AOC 1001 to become an effective treatment option for
people living with DM1, a devastating rare disease for which
there are no treatment options available. With this robust
data package, we are finalizing the Phase 3 study design and global
regulatory path for AOC 1001 and look forward to sharing a first
look at efficacy data from the MARINA-OLE study in the first half
of 2024," said Sarah Boyce,
president and chief executive officer at Avidity. "In addition to
our DM1 program, we continue to advance our DMD and FSHD clinical
development programs and plan to report data from all three of our
programs by mid-2024 while continuing to expand our discovery and
development pipeline."
In May 2023, the U.S. Food and
Drug Administration (FDA) eased the partial clinical hold on AOC
1001, allowing Avidity to double the number of participants in the
MARINA-OLE study receiving 4 mg/kg of AOC 1001 from 12 to 24
participants. Data from the 12 participants dose-escalated from 2
mg/kg to 4 mg/kg of AOC 1001 as part of the easement of the partial
clinical hold showed no neurological events and no MRI changes
following dosing. The company continues to work as quickly as
possible to resolve the partial clinical hold.
Data presented at World Muscle Society (WMS)
The Phase
1/2 MARINA trial was a randomized, double-blind, placebo-controlled
study designed to evaluate the safety and tolerability of single
and multiple ascending doses of AOC 1001 administered intravenously
in adults with DM1. Data were assessed from a 3:1 randomized study
with 38 participants who were administered one dose of 1 mg/kg of
AOC 1001, three doses of either 2 mg/kg of AOC 1001 or 4 mg/kg of
AOC 1001 (reflected as siRNA dose), or placebo. The endpoints used
in MARINA measure important aspects of the disease and correspond
to those utilized in the ongoing END-DM1 natural history study. All
37 participants that completed the MARINA trial remain on AOC 1001
in the MARINA-OLE trial. Safety and tolerability data of AOC 1001
include data from MARINA and MARINA-OLE. There were 10 participants
treated with placebo in MARINA that were newly treated with AOC
1001 in MARINA-OLE.
New AOC 1001 data demonstrate improvement in additional
functional measures augmenting previously reported positive
data that demonstrated improvements in functional assessments
of myotonia (video hand opening time, or vHOT), strength
(Quantitative Muscle Testing total score, or QMT) and mobility
(10-meter walk run test, or 10mWRT and the Timed Up and Go test, or
TUG).
New positive AOC 1001 data presented at WMS include:
- Multiple additional measures of strength:
- Hand grip
- Manual Muscle Testing (MMT) composite score
- Both upper and lower QMT composites
- 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).
New favorable long-term AOC 1001 safety and tolerability data
include data from MARINA-OLE with over 200 infusions totaling 46.2
patient-years of exposure.
- The most common AEs in the MARINA-OLE were procedural pain
(22%), pain in extremity (such as arm, leg or foot pain/soreness)
and headache (both 16%).
- There was one resolved adverse event of mild increase in liver
enzymes.
- There have been no reported AEs of anemia in the MARINA-OLE. In
the MARINA clinical program, anemia has been asymptomatic except
for one participant who did not require treatment.
- There have been no discontinuations in the MARINA-OLE
study.
In addition to evaluating AOC 1001 in the MARINA-OLE trial in
people living with DM1, Avidity is also advancing AOC 1044 in the
Phase 1/2 EXPLORE44™ trial in people living with DMD44
and plans to report data from healthy volunteers in the EXPLORE44
trial in the fourth quarter of 2023. In addition, the company is
evaluating AOC 1020 in the Phase 1/2 FORTITUDE™ trial in people
living with FSHD. Data from a preliminary assessment in
approximately half of the participants in the FORTITUDE trial is
planned for the first half of 2024.
About the Phase 1/2
MARINA® Trial
The MARINA® trial is 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 AOC 1001 administered intravenously. The MARINA
trial assessed the activity of 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
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 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 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 AOC 1001 regardless of whether
they received active treatment or placebo in the MARINA study. The
total duration of active treatment with 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 AOC 1001
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. 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, 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. 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 AOC 1001 and the
FDA has granted 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 functional data associated with AOC 1001; the
impact of such data on the advancement of AOC 1001; expectations
related to the MARINA-OLE study and AOC 1001; the anticipated
timing of release of data from the MARINA-OLE™,
EXPLORE44™ and FORTITUDE™ trials; plans for a
Phase 3 study and global regulatory path for AOC 1001; plans for
the progression of clinical programs for AOC 1001, AOC 1044 and AOC
1020 and the timing thereof; 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.
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 AOC 1001;
additional participant data related to AOC 1001 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; the success
of its preclinical studies and clinical trials for the company's
product candidates; Avidity's dependence on third parties in
connection with preclinical and clinical testing and product
manufacturing; Avidity may not realize the expected benefits of its
collaborations; regulatory developments in the United States and foreign countries;
Avidity could exhaust its available capital resources sooner than
it currently expects and fail to raise additional needed funds; and
other risks described in Avidity's Annual Report on Form 10-K for
the fiscal year ended December 31,
2022, filed with the Securities and Exchange Commission
(SEC) on February 28, 2023, 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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