SAN FRANCISCO, May 1, 2019 /PRNewswire/ -- Audentes
Therapeutics, Inc. (Nasdaq: BOLD), a leading AAV-based genetic
medicines company focused on developing and commercializing
innovative products for serious rare neuromuscular diseases, today
announced new positive data from ASPIRO, the Phase 1/2 clinical
trial of AT132 for the treatment of X-linked Myotubular Myopathy
(XLMTM). The data are being presented today at the 22nd
Annual Meeting of the American Society of Gene and Cell Therapy by
Perry B. Shieh, M.D., Ph.D.,
Associate Professor of Neurology, University
of California Los Angeles and Principal Investigator for
ASPIRO during the plenary session, "Presidential Symposium &
Presentation of the Top Abstracts," scheduled to begin at
2:15 pm ET.
"The encouraging clinical profile established by AT132 in the
ASPIRO Phase 1/2 study is further supported by the new data shared
today," stated Dr. Shieh. "Results across both dose cohorts
show clinically meaningful improvements in neuromuscular and
respiratory function, durable improvements in muscle pathology, and
progressive attainment of motor developmental milestones."
"We are excited to share today's results and are working hard
toward our goal of making AT132 available to patients living with
XLMTM globally as rapidly as possible," stated Matthew R. Patterson, Chairman and Chief
Executive Officer of Audentes. "We look forward to important
next steps for the program, including selection of the optimal dose
and further discussions with regulators in the U.S. and
Europe regarding possible pathways
to license applications."
Data Summary
The newly reported data include safety
and efficacy assessments for 11 patients enrolled in ASPIRO as of
the April 8, 2019 data cut-off date,
including 48 weeks of follow-up for seven patients enrolled in
Cohort 1 (1x1014 vector genomes per kilogram (vg/kg);
six treated and one untreated control) and 24 weeks of follow-up
for four patients in Cohort 2 (3x1014 vg/kg; three
treated and one untreated control). Key assessments include
neuromuscular function as measured by both improvements in the CHOP
INTEND score and the achievement of motor milestones; respiratory
function as measured by improvements in maximal inspiratory
pressure (MIP) and reduction in ventilator dependence; and vector
copy number, mRNA, protein expression and histological improvement
as assessed via muscle biopsy.
Efficacy
Rapid CHOP INTEND improvements have been achieved and maintained in
both dose cohorts, and the majority of patients have demonstrated
progressive attainment of motor developmental milestones, such as
head control, sitting unassisted, crawling, standing with support
and initiating stepping movements. Patients receiving AT132
have achieved reductions in ventilator dependence not previously
observed in chronically ventilated patients with neuromuscular
disorders. Reduction of ventilator dependence is an endpoint
considered to be correlated with survival. Four patients were
successfully weaned off of ventilation by the 48-week timepoint,
with all other treated patients demonstrating sustained and
clinically meaningful reductions in ventilator use.
Muscle biopsy data show robust dose-dependent transduction,
transcription and protein expression. All biopsies show
marked improvement in histopathological markers of disease, with a
trend toward continued improvement in the Cohort 1 patient samples
from 24 to 48-week timepoints, and evidence of more rapid
pathological improvement by week 24 in the Cohort 2 biopsy
samples.
Safety
AT132 has been generally well-tolerated and has shown a manageable
safety profile across both dose groups. There have been no
possibly or probably treatment-related serious adverse events
(SAEs) reported in Cohort 1 since the scientific update in May
2018. There have been eight possibly or probably
treatment-related SAEs reported in Cohort 2. All SAEs have
been successfully managed and patients have shown no evidence of
clinical compromise. Results to date indicate no clinically
meaningful differences in the safety and tolerability profile of
AT132 between the 1x1014 vg/kg and 3x1014
vg/kg dose cohorts.
Next steps in the AT132 development program include selection of
the optimal dose in the ASPIRO study, planned to occur in the
second quarter of 2019, and further interactions with the FDA and
EMA, planned to occur in the third quarter of 2019, to present this
most recent data update and gain further alignment on the license
application submission pathways for AT132 in the United States and Europe.
About X-linked Myotubular Myopathy
XLMTM is a serious,
life-threatening, rare neuromuscular disease that is characterized
by extreme muscle weakness, respiratory failure, and early death.
Mortality rates are estimated to be 50 percent in the first
18 months of life, and for those patients who survive past infancy,
there is an estimated 25% mortality by the age of 10. XLMTM
is caused by mutations in the MTM1 gene that lead to a lack or
dysfunction of myotubularin, a protein that is needed for normal
development, maturation, and function of skeletal muscle cells.
The disease affects approximately 1 in 40,000 to 50,0000
newborn males.
XLMTM places a substantial burden of care on patients, families
and the healthcare system, including high rates of healthcare
utilization, hospitalization and surgical intervention. More
than 80 percent of XLMTM patients require ventilator support, and
the majority of patients require a gastrostomy tube for nutritional
support. In most patients, normal developmental motor
milestones are delayed or never achieved. Currently, only
supportive treatment options, such as ventilator use or a feeding
tube, are available.
About AT132 for the treatment of X-linked Myotubular
Myopathy
Audentes is developing AT132, an AAV8 vector
containing a functional copy of the MTM1 gene, for the treatment of
XLMTM. AT132 may provide patients with significantly improved
outcomes based on the ability of AAV8 to target skeletal muscle and
increase myotubularin expression in targeted tissues following a
single intravenous administration. The preclinical
development of AT132 was conducted in collaboration with Genethon
(www.genethon.fr).
AT132 has been granted Regenerative Medicine and Advanced
Therapy (RMAT), Rare Pediatric Disease, Fast Track, and Orphan Drug
designations by the U.S. Food and Drug Administration (FDA), and
Priority Medicines (PRIME) and Orphan Drug designations by the
European Medicines Agency (EMA).
About Audentes Therapeutics, Inc.
Audentes
Therapeutics (Nasdaq: BOLD) is a leading AAV-based genetic
medicines company focused on developing and commercializing
innovative products for serious rare neuromuscular diseases.
We are leveraging our AAV gene therapy technology platform and
proprietary manufacturing expertise to develop programs across
three modalities: gene replacement, vectorized exon skipping, and
vectorized RNA knockdown. Our product candidates are showing
promising therapeutic profiles in clinical and preclinical studies
across a range of neuromuscular diseases. Audentes is a focused,
experienced and passionate team driven by the goal of improving the
lives of patients.
For more information regarding Audentes, please visit
www.audentestx.com.
Forward Looking Statements
This press release contains
forward-looking statements within the meaning of the "safe harbor"
provisions of the Private Securities Litigation Reform Act of 1995,
including, but not limited to, the potential benefits and
availability of AT132 for patients and the expected timing for
optimal dose selection and final agreement on regulatory submission
pathways for AT132. All statements other than statements of
historical fact are statements that could be deemed forward-looking
statements. Although the company believes that the
expectations reflected in such forward-looking statements are
reasonable, the company cannot guarantee future events, results,
actions, levels of activity, performance or achievements, and the
timing and results of biotechnology development and potential
regulatory approval is inherently uncertain. Forward-looking
statements are subject to risks and uncertainties that may cause
the company's actual activities or results to differ significantly
from those expressed in any forward-looking statement, including
risks and uncertainties related to the company's ability to advance
its product candidates, obtain regulatory approval of and
ultimately commercialize its product candidates, the timing and
results of preclinical and clinical trials, the company's ability
to fund development activities and achieve development goals, the
company's ability to protect intellectual property and other risks
and uncertainties described under the heading "Risk Factors" in
documents the company files from time to time with the Securities
and Exchange Commission. These forward-looking statements
speak only as of the date of this press release, and the company
undertakes no obligation to revise or update any forward-looking
statements to reflect events or circumstances after the date
hereof.
Audentes Contacts:
Investor Contact:
Andrew Chang
415.818.1033
achang@audentestx.com
Media Contact:
Sarah Spencer
415.957.2020
sspencer@audentestx.com
Katie Hogan
415.951.3398
khogan@audentestx.com
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