– New data showed improvements in cognition and
behavior during the first year of treatment with additional
increases demonstrated as treatment continued –
– Clinical effects observed across the Phase
1/2a and open-label extension studies (OLEs) of zorevunersen are a
first in the treatment of Dravet syndrome and support plans for the
Company’s Phase 3 registrational study –
– Zorevunersen generally well-tolerated across
the studies –
– Data presented for the first time at the 15th
European Epilepsy Congress (EEC) –
Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company
dedicated to restoring protein expression by harnessing the body’s
potential with RNA medicine, today announced highlights from
presentations at the 15th European Epilepsy Congress (EEC) related
to the Company’s work to develop the first disease-modifying
medicine for Dravet syndrome. Zorevunersen (STK-001) data showing
substantial and sustained reductions in seizures and meaningful
improvements in multiple measures of cognition and behavior were
presented for the first time in a scientific forum. New data from
an analysis of patients treated in the Phase 1/2a ADMIRAL study
showed improvements in cognition and behavior during the first year
of treatment with additional increases demonstrated as treatment
continued. In addition, data from a two-year natural history study
presented at the meeting showed that despite treatment with
standard-of-care antiseizure medications, patients with Dravet
syndrome continued to have high seizure rates and plateaued in
their neurodevelopment, resulting in a widening gap in development
compared to their neurotypical peers.
Dravet syndrome is a severe and progressive genetic epilepsy
characterized by frequent, prolonged and refractory seizures
beginning within the first year of life. The disease is classified
as a developmental and epileptic encephalopathy due to the
developmental delays and cognitive impairment associated with the
disease. There are no approved disease-modifying therapies for
people living with Dravet syndrome, which occurs in one out of
16,000 babies.
“The profound reductions in seizures and improvements in
cognition and behavior seen in these studies open the door to a new
era in the treatment of Dravet syndrome and provide convincing
evidence of the potential for zorevunersen as the first
disease-modifying medicine,” said Helen Cross, MB ChB, Ph.D.,
Professor, The Prince of Wales’s Chair of Childhood Epilepsy and
Director of University College London Great Ormond Street Institute
of Child Health, Honorary Consultant in Paediatric Neurology, and
the ADMIRAL study lead investigator. “We are very encouraged by the
data from the Phase 1/2a ADMIRAL study that showed substantial
reductions in seizures and meaningful improvements in cognition and
behavior within the first year of treatment. As patients continue
treatment in the open-label extension study we see even greater
improvements in their cognition and behavior, which is
remarkable.”
“The two-year natural history data provide clear evidence that
current anti-seizure medicines are insufficient because even with
the best available medicines patients still suffer from continued
high rates of seizures and, as these children age, their
development falls further behind their neurotypical peers,” said
Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke
Therapeutics. “Data from our clinical studies of zorevunersen
provide a glimpse into the future of treatment for patients with
Dravet syndrome. The data from our studies suggest that by
restoring protein expression with zorevunersen, we may be able to
substantially reduce seizures beyond any benefit patients are
currently receiving from anti-seizure medicines. Even more
promising is the potential to improve cognition and behavior, which
has never before been demonstrated in a clinical study of Dravet
syndrome. These data provide confidence in our plans for a Phase 3
registrational study, including the dose regimen and clinical
endpoints.”
Highlights from the Company’s presentations at the meeting
include:
- MONARCH and ADMIRAL Phase 1/2a studies [Paediatric Epileptology
Session: Tuesday, September 10 at 12:22PM CEST]: Single and
multiple doses of zorevunersen up to 70mg were generally well
tolerated. Patients treated with 2 or 3 doses of 70mg of
zorevunersen experienced median seizure reductions of 85% (n=10) at
3 months and 74% (n=9) at 6 months after the last dose, compared to
baseline. Multiple doses of zorevunersen (30mg, 45mg, or 70mg) led
to meaningful improvements in multiple measures of cognition and
behavior within the first year of treatment, including receptive
communication, interpersonal relationships and gross motor
skills.
- SWALLOWTAIL and LONGWING open label extension (OLE) studies
[Poster: P875]: Safety findings among patients who continued
treatment were consistent with the findings from the Phase 1/2a
studies, except for a greater incidence of cerebrospinal fluid
protein elevation. Durable reductions in convulsive seizure
frequency were observed throughout the course of treatment. In
addition, data indicated meaningful improvements in multiple
measures of cognition and behavior over the first year of continued
dosing of zorevunersen.
- BUTTERFLY (natural history study) [Poster: P788]: Compared to
their neurotypical peers, adaptive functioning and neurodevelopment
in patients with Dravet syndrome generally plateaued, resulting in
a widening developmental gap over time. Seizure rates remained high
over 24 months despite treatment with standard-of-care antiseizure
medications.
All presentations are available for download on the Stoke
Therapeutics website under the Investors & News tab.
About Dravet Syndrome
Dravet syndrome is a severe and progressive genetic epilepsy
characterized by frequent, prolonged and refractory seizures,
beginning within the first year of life. Dravet syndrome is
difficult to treat and has a poor long-term prognosis.
Complications of the disease often contribute to a poor quality of
life for patients and their caregivers. The effects of the disease
go beyond seizures and often include intellectual disability,
developmental delays, movement and balance issues, language and
speech disturbances, growth defects, sleep abnormalities,
disruptions of the autonomic nervous system and mood disorders. The
disease is classified as a developmental and epileptic
encephalopathy due to the developmental delays and cognitive
impairment associated with the disease. Compared with the general
epilepsy population, people living with Dravet syndrome have a
higher risk of sudden unexpected death in epilepsy, or SUDEP. There
are no approved disease-modifying therapies for people living with
Dravet syndrome. One out of 16,000 babies are born with Dravet
syndrome, which is not concentrated in a particular geographic area
or ethnic group.
About Zorevunersen (STK-001)
Zorevunersen is an investigational new medicine for the
treatment of Dravet syndrome currently being evaluated in ongoing
clinical trials. Stoke believes that zorevunersen, a proprietary
antisense oligonucleotide (ASO), has the potential to be the first
disease-modifying therapy to address the genetic cause of Dravet
syndrome. Zorevunersen is designed to upregulate NaV1.1 protein
expression by leveraging the non-mutant (wild-type) copy of the
SCN1A gene to restore physiological NaV1.1 levels, thereby reducing
both occurrence of seizures and significant non-seizure
comorbidities. Zorevunersen has been granted orphan drug
designation by the FDA and the EMA, and rare pediatric disease
designation by the FDA as a potential new treatment for Dravet
syndrome.
About the U.S. Studies: MONARCH (Phase 1/2a) and SWALLOWTAIL
(OLE)
The MONARCH study was a Phase 1/2a open-label study of children
and adolescents ages 2 to 18 who have an established diagnosis of
Dravet syndrome and have evidence of a genetic mutation in the
SCN1A gene. The primary objectives for the study were to assess the
safety and tolerability of zorevunersen (STK-001), as well as to
determine the pharmacokinetics in plasma and exposure in
cerebrospinal fluid. A secondary objective was to assess the
efficacy as an adjunctive antiepileptic treatment with respect to
the percentage change from baseline in convulsive seizure
frequency.
Following completion of MONARCH, patients who met study entry
criteria were eligible to continue treatment in SWALLOWTAIL, an
open-label extension (OLE) study designed to evaluate the long-term
safety and tolerability of repeat doses of zorevunersen. The study
is also evaluating the long-term effects of zorevunersen on
convulsive seizure frequency and on behavior, cognition and overall
quality of life. Dosing in SWALLOWTAIL is ongoing.
About the UK Studies: ADMIRAL (Phase 1/2a) and LONGWING
(OLE)
The ADMIRAL study was a Phase 1/2a open-label study of children
and adolescents ages 2 to <18 who have an established diagnosis
of Dravet syndrome and have evidence of a genetic mutation in the
SCN1A gene. The primary objectives for the study were to assess the
safety and tolerability of multiple doses of zorevunersen
(STK-001), as well as to determine the pharmacokinetics in plasma
and exposure in cerebrospinal fluid. A secondary objective was to
assess the effect of multiple doses of zorevunersen as an
adjunctive antiepileptic treatment with respect to the percentage
change from baseline in convulsive seizure frequency. Overall
clinical status and quality of life were secondary endpoints of
ADMIRAL.
Following completion of ADMIRAL, patients who met study entry
criteria were eligible to continue treatment in LONGWING, an
open-label extension (OLE) study designed to evaluate the long-term
safety and tolerability of repeat doses of zorevunersen. The study
is also evaluating the long-term effects of zorevunersen on
convulsive seizure frequency and on behavior, cognition and overall
quality of life. Dosing in LONGWING is ongoing.
About the BUTTERFLY Observational Study
The BUTTERFLY study was a multicenter, longitudinal,
prospective, observational study of children and adolescents ages 2
to 18 who have been diagnosed with Dravet syndrome as a result of
an SCN1A gene mutation. This study was designed to evaluate
neurodevelopmental status and change from baseline to 24 months.
Secondary and exploratory endpoints in the study evaluated changes
in other disease measures, including seizures and additional
non-seizure comorbidities. No investigational medications or other
treatments were provided. Participants continued to receive their
usual care, including anti-seizure medications, and were observed
for up to two years. The study was conducted at approximately 20
sites in the United States. Two-year results were presented at the
American Epilepsy Society Annual Meeting in December 2023 and
showed that, on average, patients experienced no meaningful
improvement in convulsive seizure frequency and exhibited widening
gaps in cognition and behavior compared to neurotypical peers,
despite treatment with the best available anti-seizure
medicines.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company
dedicated to restoring protein expression by harnessing the body’s
potential with RNA medicine. Using Stoke’s proprietary TANGO
(Targeted Augmentation of Nuclear Gene Output) approach, Stoke is
developing antisense oligonucleotides (ASOs) to selectively restore
protein levels. Stoke’s first compound, zorevunersen (STK-001), is
in clinical testing for the treatment of Dravet syndrome, a severe
and progressive genetic epilepsy. Dravet syndrome is one of many
diseases caused by a haploinsufficiency, in which a loss of ~50% of
normal protein levels leads to disease. Stoke is pursuing the
development of STK-002 for the treatment of autosomal dominant
optic atrophy (ADOA), the most common inherited optic nerve
disorder. Stoke’s initial focus is haploinsufficiencies and
diseases of the central nervous system and the eye, although proof
of concept has been demonstrated in other organs, tissues, and
systems, supporting its belief in the broad potential for its
proprietary approach. Stoke is headquartered in Bedford,
Massachusetts with offices in Cambridge, Massachusetts. For more
information, visit https://www.stoketherapeutics.com/.
Cautionary Note Regarding 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 ability of zorevunersen to treat the underlying
causes of Dravet syndrome and reduce seizures or show improvements
in non-seizure comorbidities and the timing and expected progress
of clinical trials, regulatory meetings and regulatory decisions.
Statements including words such as “expect,” “plan,” “will,”
“continue,” or “ongoing” and statements in the future tense are
forward-looking statements. These forward-looking statements
involve risks and uncertainties, as well as assumptions, which, if
they prove incorrect or do not fully materialize, could cause our
results to differ materially from those expressed or implied by
such forward-looking statements, including, but not limited to,
risks and uncertainties related to: the Company’s ability to
advance, obtain regulatory approval of, and ultimately
commercialize its product candidates, including zorevunersen; the
timing of data readouts and interim and final results of
preclinical and clinical trials; the receipt and timing of
potential regulatory decisions; positive results in a clinical
trial may not be replicated in subsequent trials or successes in
early stage clinical trials may not be predictive of results in
later stage trials; the Company’s ability to fund development
activities and achieve development goals; the Company’s ability to
protect its intellectual property; the direct or indirect impact of
global business, political and macroeconomic conditions, including
inflation, interest rate volatility, cybersecurity events,
uncertainty with respect to the federal budget, instability in the
global banking system and volatile market conditions, and global
events, including public health crises, and ongoing geopolitical
conflicts, such as the conflicts in Ukraine and the Middle East;
and other risks and uncertainties described under the heading “Risk
Factors” in the Company’s Annual Report on Form 10-K for the year
ended December 31, 2023, its quarterly reports on Form 10-Q, and
the other documents it 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20240910810707/en/
Stoke Media & Investor Contacts: Dawn Kalmar Chief
Communications Officer dkalmar@stoketherapeutics.com
781-303-8302
Doug Snow Director, Communications & Investor Relations
IR@stoketherapeutics.com 508-642-6485
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