SAN FRANCISCO, Jan. 4, 2018 /PRNewswire/ --
Conference call and webcast January 4, 2018 at 8:00am
EST
Webcast may be accessed via the Investor and
Media page of the Audentes website
Call may be accessed
by dialing 1-833-659-8620 and using conference ID#: 4957669
Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology
company focused on developing and commercializing gene therapy
products for patients living with serious, life-threatening rare
diseases, today announced positive interim data from the first dose
cohort of ASPIRO, a Phase 1/2 clinical trial of AT132 in patients
with X-Linked Myotubular Myopathy (XLMTM). ASPIRO is a
multicenter, multinational, open-label, ascending dose study to
evaluate the safety and preliminary efficacy of AT132 in
approximately 12 XLMTM patients less than five years of
age.
"The early AT132 efficacy data observed in our first dose cohort
of patients have exceeded our expectations," stated Dr.
Suyash Prasad, Senior Vice President
and Chief Medical Officer of Audentes. "At the 12-week timepoint,
Patient 1 has improved from a severely compromised baseline to
achieve a CHOP-INTEND score and maximal inspiratory pressure that
are approaching the ranges normally seen in healthy children.
Importantly, Patient 1 has also attained several age-appropriate
developmental milestones within this time period, including
head-control, rolling over and sitting unassisted. While
still early in the trial, we view these initial efficacy data as a
promising indicator of the potential for AT132 to bring meaningful
benefit to patients and families living with this devastating
disease."
ASPIRO Interim Data Summary
The interim data includes
safety and efficacy assessments for the first dose cohort of
ASPIRO, comprised of three AT132-treated patients dosed at
1x1014 vector genomes (vg) per kilogram (kg), and one
delayed-treatment control patient. As of December 21, 2017, individual patient follow-up
ranged from 4 to 12 weeks.
Safety Summary
There have been a total of six adverse
events (AEs) reported in ASPIRO, two of which were determined to be
serious adverse events (SAEs). Both SAEs occurred in Patient
3, the first of which was a hospitalization one week
post-administration due to pneumonia and was deemed not
treatment-related. Patient 3 was also hospitalized at week 7
post-administration due to a gastrointestinal infection and
elevated troponin levels, the latter of which was deemed probably
treatment-related and is responding to treatment with intravenous
steroid administration and supportive care.
Of the four non-serious AEs, two have been determined to be
probably or possibly treatment-related. Patient 1 experienced
a mild, clinically asymptomatic exacerbation of a preexisting
elevated bilirubin level, which was deemed possibly
treatment-related and resolved with treatment. Patient 2
experienced a clinically asymptomatic elevation in liver enzyme
levels toward the end of the protocol-specified prednisolone
weaning period, which was deemed to be probably treatment-related
and was controlled by extending the duration of steroid
coverage.
Efficacy Summary
The key assessment of neuromuscular
function in this first data set from Cohort 1 is the CHOP-INTEND
scale, in which a maximal score of 64 reflects the level of
neuromuscular function that a healthy baby is expected to approach
by 3-6 months of age. Additional analyses to be reported based on
longer term follow-up include the MFM-20 and Bayley-III™ scales of
infant and toddler development (fine and gross motor function).
Motor developmental milestones are captured within each of the
neuromuscular assessments.
The key assessment of respiratory function in this first data
set from Cohort 1 is a measurement of maximal inspiratory pressure
(MIP), for which values ≥ 80 cmH20 are considered normal
in healthy children less than 5 years of age. Additional analyses
to be reported based on longer term follow-up include measurement
of maximal expiratory pressure (MEP), time per day on invasive
ventilatory support (tracheostomy) or non-invasive respiratory
support (BiPAP), and for those patients who are on 24-hour
continuous ventilatory support, an assessment of ability to
maintain adequate respiratory function while off a ventilator,
termed "respiratory sprinting."
Patient Interim Data Summaries:
- Patient 1: data set includes assessments through week 12
timepoint
-
- Age 0.8 years (9 months) and on 12 hours of BiPAP per day at
baseline
- CHOP-INTEND increased from 29 at baseline to 56 at week 12
- MIP increased from 33 cmH20 at baseline to 80
cmH20 at week 12
- No age-appropriate first-year motor milestones were achieved at
the baseline assessment; by week 12, Patient 1 had acquired several
age appropriate skills, including the ability to control head
movements, roll over by himself and sit unassisted for > 5
seconds
- Patient 2: data set includes assessments through week 8
timepoint
-
- Age 4.1 years and on 17 hours of invasive ventilation per day
at baseline
- CHOP-INTEND increased from 45 at baseline to 56 at week 8
- MIP increased from 44 cmH20 at baseline to 77
cmH20 at week 4
- Patient 3: data set includes assessments through week 4
timepoint
-
- Age 2.6 years and on continuous (24-hour) invasive ventilation
at baseline
- CHOP-INTEND did not change meaningfully from 34 at baseline to
36 at week 4
- MIP increased from 26 cmH20 at baseline to 44
cmH20 at week 4
- Patient 4 (delayed-treatment control): data set includes
assessments through week 4 timepoint
-
- Age 4.0 years and on 12 hours of BiPAP per day at baseline
- CHOP-INTEND did not change meaningfully from 49 at baseline to
46 at week 4
- MIP at baseline was 58 cmH20; MIP was not assessed
at week 4 per protocol
Physicians and caregivers have reported progressive qualitative
improvements in disease severity in all treated patients.
Ventilator settings (pressure, rate and volume of mechanical
ventilation) have been reduced in Patients 1 and 2. All treated
patients have demonstrated improvements in airway clearance
control, including swallowing and coughing, which is critical to
preventing aspiration. By way of example, at baseline Patient 1
required suctioning of the oro-pharyngeal cavity several times per
hour, and by week 12 he required no suctioning. In addition,
investigators report anecdotally that all treated patients have
increased limb and trunk strength, which is an early indicator of
gross motor function improvement, and that the velocity and
accuracy of their movements have increased. Caregivers also report
that patients have increased vocalization, improving their ability
to communicate.
"Physician and caregiver reports of patient progress are an
important complement to the formal neuromuscular and respiratory
data being collected," stated Dr. Prasad. "These qualitative
assessments of the child's overall disease state and degree of
change between visits provide further insight into the impact of
AT132 on the XLMTM disease course."
Audentes is currently reviewing the interim efficacy and safety
data with the independent Data Monitoring Committee of ASPIRO prior
to initiating enrollment and dosing of the next cohort.
Audentes plans to provide the next update on interim data
from ASPIRO in the second quarter of 2018.
"This is a promising start to ASPIRO," stated Matthew R. Patterson, President and Chief
Executive Officer of Audentes. "While the data are preliminary, we
are very encouraged and will continue to advance this important
work as rapidly as possible, keeping in mind our goal of bringing a
potentially transformative treatment to patients living with this
devastating disease."
Conference Call
At 8:00 a.m. Eastern
Time today, Audentes management will host a conference call
and a simultaneous webcast to discuss the interim data from the
first dose cohort of ASPIRO. To access a live webcast of the
conference call, please visit the Investor and Media page of the
Audentes website at www.audentestx.com. Alternatively, please
call 1-833-659-8620 (U.S.) or 1-409-767-9247 (international) and
dial the conference ID 4957669 to access the call. A replay
of the webcast will be available on the Audentes website for
approximately 30 days.
About ASPIRO, the Phase 1/2 Clinical Study of
AT132
ASPIRO is a multicenter, multinational, open-label,
ascending dose study to evaluate the safety and preliminary
efficacy of AT132 in approximately 12 XLMTM patients less than five
years of age. The study is designed to include nine AT132 treated
subjects and three delayed-treatment concurrent control subjects,
who will be treated after the optimal dose is selected.
Primary endpoints include safety (adverse events and certain
laboratory measures) and efficacy (assessments of neuromuscular and
respiratory function). Secondary endpoints include the burden
of disease and health related quality-of-life, and muscle tissue
histology and biomarkers. The primary efficacy analysis is
expected to be conducted at 12 months, with interim evaluations to
be conducted at earlier time points. After the primary 12-month
assessment, subjects are expected to be followed for another four
years to assess long term safety, durability of effect and
developmental progression.
About AT132 for X-Linked Myotubular Myopathy
AT132 is
the Audentes product candidate being developed to treat XLMTM, a
rare monogenic disease characterized by extreme muscle weakness,
respiratory failure and early death, with an estimated 50%
mortality rate by 18 months of age. XLMTM is caused by
mutations in the MTM1 gene, which encodes the protein
myotubularin. Myotubularin plays an important role in the
development, maintenance and function of skeletal muscle
cells. AT132 is comprised of an AAV8 vector containing a
functional copy of the MTM1 gene. In January 2018, Audentes reported positive interim
data from the first dose cohort of ASPIRO, a multicenter, ascending
dose Phase 1/2 clinical study to evaluate the safety and
preliminary efficacy of AT132 in approximately 12 XLMTM patients
less than five years of age. The preclinical development of AT132
was conducted in collaboration with Genethon (www.genethon.fr).
About Audentes Therapeutics, Inc.
Audentes
Therapeutics (Nasdaq: BOLD) is a clinical-stage biotechnology
company focused on developing and commercializing gene therapy
products for patients living with serious, life-threatening rare
diseases. We are currently conducting a Phase 1/2 clinical
study of our lead product candidate AT132 for the treatment of
X-Linked Myotubular Myopathy (XLMTM) and have three additional
product candidates in development, including AT342 for the
treatment of Crigler-Najjar Syndrome, AT982 for the treatment of
Pompe disease, and AT307 for the treatment of the CASQ2 subtype of
Catecholaminergic Polymorphic Ventricular Tachycardia
(CASQ2-CPVT). We are a focused, experienced and passionate
team committed to forging strong, global relationships with the
patient, research and medical communities.
For more information regarding Audentes, please
visit www.audentestx.com.
About Genethon
Genethon, located in Evry, France, is a non-profit R&D organization
dedicated to the development of biotherapies for orphan genetic
diseases, from research to clinical validation. Genethon is
specialized in the discovery and development of gene therapy drugs
and has multiple ongoing programs at clinical, preclinical and
research stage for neuromuscular, blood, immune system, liver and
eye diseases.
Discover Genethon's pipeline:
http://www.genethon.fr/produits/
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: enrollment, dose and timing of the
second cohort in ASPIRO and the clinical results from ASPIRO.
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 commercial 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, Investor Relations
415.818.1033
ir@audentestx.com
Media Contact:
Paul Laland
415.519.6610
media@audentestx.com
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