SAN FRANCISCO, May 16, 2018 /PRNewswire/ -- 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 continuing positive 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 data were presented during an oral presentation at the
21st annual meeting of the American Society of Gene and
Cell Therapies in Chicago, IL.
"We continue to be highly encouraged by the profile of AT132
observed to date in the ASPIRO study," stated Dr. Suyash Prasad, Senior Vice President and Chief
Medical Officer of Audentes. "Patients treated in the initial
cohort continue to make advancements in neuromuscular and
respiratory function, highlighted by the fact that our earliest
treated patient has now been ventilator independent for over eight
weeks."
Dr. Prasad continued, "We are pleased to see the encouraging
trends in safety and efficacy continue in the recently enrolled
Cohort 1 expansion patients, with early gains in CHOP-INTEND and
MIP observed by the four-week timepoint and no significant
treatment-related adverse events reported to date. We remain
inspired by our patients and their families, and we look forward to
continuing our work with the XLMTM community to advance this
important work as rapidly as possible."
ASPIRO Interim Data Summary
The interim data includes
safety and efficacy assessments as of May
12, 2018 for the first dose cohort of ASPIRO, comprised of
six AT132-treated patients dosed at 1x1014 vector
genomes (vg) per kilogram (kg), and one delayed-treatment
concurrent control patient. Individual patient follow-up
ranged up to 24 weeks.
Safety Summary
There have been a total of 24 adverse
events (AEs) reported in ASPIRO, six of which were determined to be
serious adverse events (SAEs).
One of the six SAEs occurred in Patient 4, the delayed treatment
concurrent control patient, who was hospitalized for
gastroenteritis at week 10. The patient has recovered and the event
was determined to be not treatment-related. The remaining
five SAEs occurred in Patient 3. The first was a hospitalization
for pneumonia two weeks post study drug administration (not
treatment-related); the next three were a series of related SAEs
that occurred seven weeks post study drug administration and
included hospitalization for a gastrointestinal infection during
which the patient experienced elevated creatine kinase (CK) and
troponin levels suggestive of myocarditis (probably
treatment-related). These events have been controlled with
treatment, and cardiac function has not been compromised. The final
SAE in Patient 3 was a hospitalization at week 21 for monitoring of
atrial tachycardia, deemed possibly treatment-related.
Patient 3 was noted to have experienced an episode of tachycardia
prior to enrollment in ASPIRO.
Patient 1 experienced three non-serious AEs that were determined
to be possibly treatment-related, including mild, clinically
asymptomatic exacerbation of pre-existing hyperbilirubinemia
(resolved) and mild unspecific abnormalities in liver ultrasound
and proteinuria (resolved). Patient 2 experienced four
non-serious AEs determined to be probably treatment related,
including clinically asymptomatic hyperbilirubinemia; and liver
enzyme and CK elevations which have been controlled by extended
steroid coverage.
There have been an additional 11 non-serious AEs in ASPIRO, all
determined to be not treatment-related. There have been no
significant treatment-related adverse events identified to date in
Patients 5 through 7, referred to as the Cohort 1 expansion
patients.
Efficacy Summary
The key assessment of neuromuscular
function 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 three to six months of age. Additional
analyses to be reported based on longer term follow-up include the
Motor Function Measure (MFM-20) and Bayley-III™ scales of infant
and toddler development. Motor developmental milestones are derived
from each of the neuromuscular assessments.
The key assessment of respiratory function is a measurement of
maximal inspiratory pressure (MIP), for which values ≥ 80
cmH20 are considered normal in healthy children less
than five years of age. Additional assessments include measurement
of maximal expiratory pressure (MEP), and time per day on invasive
ventilatory support (tracheostomy) or non-invasive respiratory
support (BiPAP).
Patient Interim Data Summaries:
- Patient 1: data set includes assessments through week 24
timepoint
-
- Age 0.8 years at baseline
- BiPAP of 12 hours per day at baseline, now ventilator
independent since week 16
- CHOP-INTEND increased from 29 at baseline to 64 at week 24, an
increase of 121%
- MIP increased from 33 cmH20 at baseline to 89
cmH20 at week 24, an increase of 170%
- 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, and maintained these skills through week 24.
- Physicians and caregivers have reported additional observations
in Patient 1 at week 24, including the ability to feed orally,
stand with support and increased loudness of vocalization.
- Patient 2: data set includes assessments through week 24
timepoint
-
- Age 4.1 years at baseline
- Invasive ventilation 22 hours per day at baseline, decreased to
12 hours per day at week 24
- CHOP-INTEND increased from 45 at baseline to 59 at week 24, an
increase of 31%
- MIP increased from 44 cmH20 at baseline to 104
cmH20 at week 24, an increase of 136%
- No age-appropriate first-year motor milestones were achieved at
the baseline assessment. By week 12, Patient 2 had acquired several
skills, including the ability to control head movements, roll over
by himself and sit unassisted for > 5 seconds, and maintained
these skills through week 24.
- Physicians and caregivers have reported additional observations
in Patient 2 at week 24, including standing with support, scooting
and crawling, and increased loudness of vocalization.
- Patient 3: data set includes efficacy assessments through week
12 timepoint
-
- Age 2.6 years at baseline
- Invasive ventilation of 24 hours per day at baseline, no change
at week 12
- CHOP-INTEND increased from 34 at baseline to 43 at week 12, an
increase of 26%
- MIP increased from 26 cmH20 at baseline to 48
cmH20 at week 12, an increase of 85%
- No age appropriate first-year developmental milestones were
achieved at the baseline assessment or by week 12
- Physicians and caregivers have reported increased loudness of
vocalization and trunk strength at week 12
- Patient 4 (Delayed-treatment concurrent control): includes
assessments through week 24 timepoint
-
- Age 4.0 years at baseline
- BiPAP was 12 hours per day at baseline, no change at week
24
- CHOP-INTEND was 49 at baseline, no change at week 24
- MIP decreased from 58 cmH20 at baseline to 46
cmH20 at week 24, a decrease of 21%
- First-year developmental milestones of head control and sitting
unassisted for > 5 seconds were noted at baseline, but only head
control was maintained at week 24
- Patient 5: data set includes assessments through week four
timepoint
-
- Age 1.0 year at baseline
- Invasive ventilation of 22.7 hours per day at baseline
- CHOP-INTEND increased from 36 at baseline to 50 at week four,
an increase of 39%
- MIP increased from 14 cmH20 at baseline to 33
cmH20 at week four, an increase of 136%
- Patient 6: data set includes assessments through week four
timepoint
-
- Age 0.8 years at baseline
- Invasive ventilation of 24 hours per day at baseline, 21 hours
per day at week four
- CHOP-INTEND increased from 39 at baseline to 43 at week four,
an increase of 10%
- MIP improved 35 cmH20 at baseline to 63
cmH20 at week one, an increase of 80
- Patient 7: data set includes only baseline assessments
-
- Age 0.8 years at baseline
- Invasive ventilation of 23.5 hours per day at baseline
- CHOP-INTEND was 43 at baseline
- MIP was 29 cmH20 at baseline
Audentes is currently completing analysis of the muscle biopsies
gathered from initial Cohort 1 patients. These data, along
with the safety and efficacy assessments from all patients, will be
reviewed with the independent Data Monitoring Committee to inform
decisions regarding dose escalation. Audentes expects to
provide an update on these plans in the third quarter of 2018.
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 May 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).
AT132 has been granted orphan drug designation in both
the United States and European Union, and Rare Pediatric
Disease and Fast Track designations by the FDA.
About Audentes Therapeutics, Inc.
Audentes
Therapeutics (Nasdaq: BOLD) is a biotechnology company focused
on developing and commercializing innovative gene therapy products
for patients living with serious, life-threatening rare
diseases. We are currently conducting Phase 1 /
2 clinical studies of our lead product candidates AT132 for
the treatment of X-Linked Myotubular Myopathy (XLMTM) and AT342 for
the treatment of Crigler-Najjar Syndrome. We have two
additional product candidates in development, including 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
Created by the AFM-Telethon, the French
Muscular Dystrophy Association (AFM), Genethon, located in Evry,
France, is a non-profit R&D
organization dedicated to the development of biotherapies for
orphan genetic diseases, from the 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, and liver diseases.
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 expected benefits of the
company's product candidates, the timing and nature of clinical
development activities and anticipated clinical milestones.
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
415.818.1033
achang@audentestx.com
Media Contact:
Paul Laland
415.519.6610
plaland@audentestx.com
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