Axovant Gene Therapies Ltd. (NASDAQ: AXGT), a clinical-stage
company developing innovative gene therapies, today announced
preliminary data from an expanded access study administering
investigational AXO-AAV-GM2 gene therapy in two patients with
infantile Tay-Sachs disease (TSD) at the 27th Annual Congress of
the European Society of Gene and Cell Therapy. Infantile TSD, a
rapidly progressive and fatal pediatric neurodegenerative genetic
disorder, has a median life expectancy of approximately 3-4 years.
This data indicates the potential to modify the rate of disease
progression in children with infantile TSD.
“Today’s exciting clinical results from the
AXO-AAV-GM2 program are the first reported evidence for potential
disease modification in Tay-Sachs disease, and suggest an
opportunity for gene replacement therapy to improve outcomes for
children with this devastating condition,” said Dr. Gavin Corcoran,
chief R&D officer at Axovant. “Myelination is an important
component of healthy brain development in infants and is often
abnormal in children with Tay-Sachs disease. We were encouraged to
see MRI evidence of preserved brain architecture and improved
myelination in the early symptomatic child treated at 10 months of
age, coupled with stability of neuromuscular function as measured
on the CHOP INTEND scale. We look forward to Dr. Terry Flotte’s
presentation of this data at the ESGCT conference where he will
describe these two clinical cases in detail.”
Key findings from this first-in-human study in
patients treated with AXO-AAV-GM2, an investigational gene therapy
designed to restore β-Hexosaminidase A enzyme activity in the
central nervous system, include:
- AXO-AAV-GM2 was successfully administered in both patients and
has been generally well-tolerated to date, with no serious adverse
events or clinically-relevant laboratory abnormalities related to
therapy.
- First child with advanced infantile TSD, dosed in November
2018, is clinically stable at 41 months of age (11 months after
dosing). Patient had severe, advanced disease at time of dosing.
- Route of administration included cisterna magna (CM) and lumbar
region delivery via intrathecal catheter. Intra-thalamic dosing was
not possible due to the patient’s advanced disease.
- Observed maintenance of motor skills, as measured by the
Children's Hospital of Philadelphia Infant Test of Neuromuscular
Disorders (CHOP INTEND*), with baseline total score of 14 increased
to a total score of 18 at month 6 following gene transfer and
ranged between 14-18 from week 1 to month 6 (latest data point
collected).
- Hex A enzyme activity in cerebrospinal fluid (CSF) increased by
approximately 3-fold at month 3 and month 6 relative to
baseline.
- Second child with infantile-onset TSD, dosed in June 2019, is
clinically stable at 11 months of age (4 months after dosing).
Patient was dosed with gene therapy prior to onset of severe
symptoms.
- The route of administration was bilateral intraparenchymal
thalamic and intracisternal/intrathecal.
- Clinical disease stabilization was observed in the treated
child, with attainment of normal developmental milestones and a
normal neurologic exam at 10 months of age.
- No seizure activity and no exaggerated startle responses were
observed.
- By contrast, the patient’s untreated, two older siblings with
TSD exhibited rapid disease progression, clinical regression and
seizure onset at 10-12 months of age.
- Brain MRI taken at 10 months of age demonstrated normal brain
anatomy and increased myelination, consistent with normal brain
development at this age.
- By contrast, commonly reported MRI findings in infantile TSD at
this age include demyelination and cerebral and cerebellar
atrophy.
- CHOP INTEND total score was 58 at baseline, increased to a
total score of 60 at month 3 following gene transfer and ranged
between 58-61 from week 2 to month 3.
- Hex A enzyme activity in CSF increased to 1.8% of normal enzyme
activity between baseline and 3 months (a sustained level ≥ 0.5% of
normal enzyme activity is expected to correlate with a clinically
meaningful effect).
*CHOP INTEND is a 16-item scale of motor
function that has been validated in infants with neuromuscular
disorders. Items of motor function are graded from 0 to 4 for
each item, where zero equals no response, and 4 equals a complete
response. Change from baseline in total score of ≥ 4 points or a
total score sustained > 40 points has been associated with a
clinically meaningful benefit.
Dr. Terence Flotte, Professor of Pediatrics and
Dean at the School of Medicine, University of Massachusetts Medical
School, said, “Bilateral intrathalamic and intrathecal delivery of
rAAV gene therapy may surmount the obstacle of providing widespread
distribution of therapeutic enzyme throughout the brain and CNS.
This innovative delivery could overcome one of the primary
challenges for developing treatments for Tay-Sachs, Sandhoff and
many other severe pediatric genetic disorders, providing much
needed hope for these families.”
Dr. Flotte will present this data on AXO-AAV-GM2
in the First-in-Human gene therapy session on October 23, 2019 at
5:30 PM Central European Time (CET).
About AXO-AAV-GM2
AXO-AAV-GM2 is an investigational gene therapy
for Tay-Sachs and Sandhoff disease, which rare and fatal pediatric
neurodegenerative genetic disorders within the GM2 gangliosidosis
family, caused by defects in the HEXA (leading to
Tay-Sachs disease) or HEXB (leading to Sandhoff disease)
genes that encode the two subunits of the β-hexosaminidase A (HexA)
enzyme. Both forms of GM2 gangliosidosis are caused by overwhelming
storage of GM2 ganglioside within neurons throughout the central
nervous system), which is normally degraded in the lysosome by the
isozyme HexA. These genetic defects lead to progressive
neurodegeneration and shortened life expectancy. AXO-AAV-GM2 aims
to restore HexA levels by introducing a functional copy of
the HEXA and HEXB genes via delivery of two
co-administered AAVrh8 vectors.
In 2018, Axovant licensed exclusive worldwide
rights from the University of Massachusetts Medical School for the
development and commercialization of gene therapy programs for GM1
gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and
Sandhoff diseases.
About Axovant Gene
Therapies
Axovant Gene Therapies, part of the Roivant
family of companies, is a clinical-stage gene therapy company
focused on developing a pipeline of innovative product candidates
for debilitating neurological and neuromuscular diseases. Our
current pipeline of gene therapy candidates targets GM1
gangliosidosis, GM2 gangliosidosis (including Tay-Sachs disease and
Sandhoff disease), and Parkinson’s disease.
Axovant is focused on accelerating product
candidates into and through clinical trials with a team of experts
in gene therapy development and through external partnerships with
leading gene therapy organizations. For more information,
visit www.axovant.com.
About Roivant
Roivant aims to improve health by rapidly
delivering innovative medicines and technologies to
patients. Roivant does this by building Vants –
nimble, entrepreneurial biotech and healthcare companies with a
unique approach to sourcing talent, aligning incentives, and
deploying technology to drive greater efficiency in R&D and
commercialization. Roivant today is comprised of a central
technology-enabled platform and 20 Vants with over 45
investigational medicines in clinical and preclinical development
and multiple healthcare technologies. For more information, please
visit www.roivant.com.
About the University of Massachusetts
Medical School
The mission of the University of Massachusetts
Medical School is to advance the health and well-being of the
people of the commonwealth and the world through pioneering
education, research, public service and health care delivery.
Research into potential therapies for lysosomal
storage diseases such as Tay-Sachs, Sandhoff disease and GM1
gangliosidosis at UMass Medical School and Auburn University has
led to significant advances in the field. Miguel Sena-Esteves, PhD,
associate professor of neurology at UMass Medical School; Heather
Gray-Edwards, PhD, DVM, formerly of Auburn and currently assistant
professor of radiology at UMass Medical School; and Douglas Martin,
PhD, professor of anatomy, physiology and pharmacology in the
College of Veterinary Medicine and the Scott-Ritchey Research
Center at Auburn University, have worked collaboratively for more
than a decade on animal models and therapeutic approaches for these
and similar disorders. For more information, visit
www.umassmed.edu.
Forward Looking Statements and
Information
This press release contains forward-looking
statements for the purposes of the safe harbor provisions under The
Private Securities Litigation Reform Act of 1995 and other federal
securities laws. The use of words such as “may,” “might,” “will,”
“would,” “should,” “expect,” “believe,” “estimate,” and other
similar expressions are intended to identify forward-looking
statements. For example, all statements Axovant makes regarding the
initiation, timing, progress, and reporting of results of its
preclinical programs, clinical trials, and research and development
programs; cash to be used in operating activities; its ability to
advance its gene therapy product candidates into and successfully
initiate, enroll, and complete clinical trials; the potential
clinical utility of its product candidates; its ability to continue
to develop its gene therapy platforms; its ability to develop and
manufacture its products and successfully transition manufacturing
processes; its ability to perform under existing collaborations
with, among others, Oxford Biomedica, and the University of
Massachusetts Medical School, and to add new programs to its
pipeline; its ability to enter into new partnerships or
collaborations; its ability to retain and successfully integrate
its leadership and personnel; and the timing or likelihood of its
regulatory filings and approvals are forward-looking. All
forward-looking statements are based on estimates and assumptions
by Axovant’s management that, although Axovant believes to be
reasonable, are inherently uncertain. All forward-looking
statements are subject to risks and uncertainties that may cause
actual results to differ materially from those that Axovant
expected. Such risks and uncertainties include, among others,
the initiation and conduct of preclinical studies and clinical
trials; the availability of data from clinical trials; the
expectations for regulatory submissions and approvals; the
continued development of its small molecule and gene therapy
product candidates and platforms; Axovant’s scientific approach and
general development progress; and the availability or commercial
potential of Axovant’s product candidates. These statements are
also subject to a number of material risks and uncertainties that
are described in Axovant’s most recent Quarterly Report on Form
10-Q filed with the Securities and Exchange
Commission on August 9, 2019, as updated by its
subsequent filings with the Securities and Exchange
Commission. Any forward-looking statement speaks only as of the
date on which it was made. Axovant undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events or otherwise.
Contacts:
Media and Investors
Parag MeswaniAxovant Gene Therapies (212)
547-2523investors@axovant.commedia@axovant.com
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