– Data from clinical studies of STK-001
demonstrated clinical benefit for patients ages 2 to 18 years old,
including reductions in seizures and improvements in cognition and
behavior that support the potential for disease modification –
– Analysis of 72 patients treated in STK-001
clinical trials suggests that higher STK-001 drug exposure in brain
leads to greater seizure reductions –
– Two-year data from the longest prospective
natural history study of Dravet syndrome showed that, on average,
patients experienced no meaningful improvement in convulsive
seizure frequency and exhibited widening gaps in cognition and
behavior despite treatment with the best available anti-seizure
medicines –
Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company
dedicated to addressing the underlying cause of severe diseases by
upregulating protein expression with RNA-based medicines, today
announced highlights from presentations of clinical data at the
American Epilepsy Society (AES) 2023 Annual Meeting December 1 – 5,
in Orlando, Florida. Together, these data support the company’s
continued progress to develop STK-001 as the first
disease-modifying medicine for the treatment of Dravet
syndrome.
“The comprehensive set of data being presented at AES are giving
us a very good understanding of how STK-001 works and its potential
to address not only seizures, but many of the non-seizure effects
of Dravet syndrome,” said Barry Ticho, M.D., Ph.D., Chief Medical
Officer of Stoke Therapeutics. “The substantial and sustained
reductions in seizure frequency and improvements in cognition and
behavior observed in our STK-001 clinical studies give us
confidence that we are addressing the root cause of Dravet
syndrome. In addition, the correlation between higher STK-001
exposure levels in brain and reductions in seizure frequency shown
in our modeling data provides additional confidence in the clinical
benefits observed among patients treated with STK-001 at higher
doses and for longer periods of time. These findings are in stark
contrast to the data from our two-year natural history study that
show a lack of improvement among patients who are taking the best
available anti-seizure medicines.”
“Dravet syndrome goes far beyond seizures, and as children grow
up, they experience a complex array of life-altering challenges,
including developmental delays, movement and balance issues and
delayed language and speech,” said Joseph Sullivan, M.D., FAES,
Professor of Neurology and Pediatrics and Director of the Pediatric
Epilepsy Center of Excellence at the University of California San
Francisco, and a prominent researcher in Dravet syndrome. “On
average, patients enrolled in the BUTTERFLY natural history study
were taking 3.5 anti-seizure medicines. Despite this, they
continued to experience similarly high rates of seizure frequency
throughout the study and fell further and further behind their
neurotypical peers in aspects of cognition and behavior, including
their ability to communicate and use gross motor and fine motor
skills. These findings highlight the critical need for a new
approach to treating this disease, one that can improve the
treatment of seizures and go beyond that to address the
debilitating cognitive and behavioral aspects of this disease.”
Highlights from the Company’s presentations of data at the
meeting, include:
- BUTTERFLY Natural History Study of Patients with Dravet
Syndrome Ages 2 to 18: Despite treatment with the best available
anti-seizure medicines, on average, patients continued to
experience convulsive seizures over 24 months at similar frequency
to baseline. No statistically significant change from baseline in
the majority of Vineland-III measures (an established instrument
for assessing developmental disabilities) was observed and the rate
of improvement on multiple clinical measures, including key domains
of the Vineland-III, was substantially below neurotypical peers.
Gaps in neurodevelopment continued to widen throughout the study
among patients with Dravet syndrome compared to their age-matched
neurotypical peers.
- MONARCH & ADMIRAL Interim Analyses: Single and multiple
doses of STK-001 up to 70mg were generally well tolerated. The
multiple dose 70mg cohort showed the greatest reductions in
convulsive seizure frequency, outperforming all lower dose groups.
Patients treated with 2 or 3 initial doses of 70mg experienced
substantial and sustained reductions in convulsive seizure
frequency.
- SWALLOWTAIL & LONGWING Open Label Extension (OLE) studies:
Approximately 90% of patients who completed participation in Phase
1/2a studies of STK-001 enrolled in one of these OLE studies.
Multiple doses of STK-001 up to 45mg given every 4 months were
generally well tolerated. In addition to durable reductions in
convulsive seizure frequency throughout the course of treatment,
data indicated substantial improvements in multiple assessments of
cognition and behavior over 12 months. These data support the
potential for disease-modification with STK-001.
- PK Model for STK-001: A relationship between STK-001 brain
exposures and convulsive seizure frequency was evaluated based on
72 patients treated in the Phase 1/2a studies (MONARCH and ADMIRAL)
and the SWALLOWTAIL OLE study in children and adolescents with
Dravet syndrome. The exposure-seizure analysis demonstrated that
higher STK-001 brain exposure leads to greater reductions in
convulsive seizure frequency (R=-0.23, P<0.001).
Details of the Company’s presentations can be found in the table
below. All presentations are available for download on the Stoke
Therapeutics website under the Investors & News tab.
Title
Presenter
Date
24-Month Analysis of BUTTERFLY: A
Prospective, Observational Study to Investigate Cognition and Other
Non-seizure Comorbidities in Children & Adolescents with Dravet
Syndrome (DS)
Joseph Sullivan, M.D., FAES,
Professor of Neurology and Pediatrics and Director of the Pediatric
Epilepsy Center of Excellence at the University of California San
Francisco
Poster Number: 1.233
Saturday, Dec. 2
12:00 PM EST
Oral Presentation:
Monday, Dec. 4
3:15 PM EST
MONARCH & ADMIRAL: Phase 1/2a
Studies in US & UK Investigating Safety and Drug Exposure of
STK-001, an Antisense Oligonucleotide (ASO), in Children &
Adolescents with Dravet Syndrome (DS)
Helen Cross, MB ChB, Ph.D.,
Professor, The Prince of Wales’s Chair of Childhood Epilepsy and
Head of the Developmental Neuroscience Programme at University
College London Great Ormond Street Institute of Child Health,
Honorary Consultant in Paediatric Neurology, President of the
International League Against Epilepsy
Poster Number: 1.276
Saturday, Dec. 2
12:00 PM EST
SWALLOWTAIL & LONGWING:
Open-Label Extension (OLE) Studies for Children and Adolescents
with Dravet Syndrome (DS) who Previously Participated in a Study of
Antisense Oligonucleotide (ASO) STK-001
Archana Desurkar M.D., Consultant
Paediatric Neurologist at Sheffield Children’s Hospital National
Health Service Foundation Trust
Poster Number: 1.279
Saturday, Dec. 2
12:00 PM EST
Utilization of a Pharmacokinetic
(PK) Model for STK-001 in Patients with Dravet Syndrome (DS) To
Support Selection of Dosing Regimens in Clinic
Meena, Ph.D., Senior Vice
President of Translational DMPK and Clinical Pharmacology at Stoke
Therapeutics
Poster Number: 3.110
Monday, Dec. 4
12:00 PM EST
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 STK-001
STK-001 is an investigational new medicine for the treatment of
Dravet syndrome currently being evaluated in ongoing clinical
trials. Stoke believes that STK-001, a proprietary antisense
oligonucleotide (ASO), has the potential to be the first
disease-modifying therapy to address the genetic cause of Dravet
syndrome. STK-001 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. STK-001 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 Phase 1/2a MONARCH Study (United States)
The MONARCH study is 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 are to assess the
safety and tolerability of STK-001, as well as to determine the
pharmacokinetics in plasma and exposure in cerebrospinal fluid. A
secondary objective is to assess the efficacy as an adjunctive
antiepileptic treatment with respect to the percentage change from
baseline in convulsive seizure frequency. Stoke also intends to
measure non-seizure aspects of the disease, such as quality of
life, as secondary endpoints. Additional information about the
MONARCH study can be found at https://www.monarchstudy.com/.
Patients who participated in the MONARCH study and meet study
entry criteria are 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 STK-001. We
expect that SWALLOWTAIL will also provide valuable information on
the preliminary effects of STK-001 on seizures along with
non-seizure aspects of the disease, such as quality of life and
cognition.
Enrollment and dosing in SWALLOWTAIL are ongoing.
About the Phase 1/2a ADMIRAL Study (United Kingdom)
The ADMIRAL study is 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 are to assess the
safety and tolerability of multiple doses of STK-001, as well as to
determine the pharmacokinetics in plasma and exposure in
cerebrospinal fluid. A secondary objective is to assess the effect
of multiple doses of STK-001 as an adjunctive antiepileptic
treatment with respect to the percentage change from baseline in
convulsive seizure frequency. Stoke also intends to measure
non-seizure aspects of the disease, such as overall clinical status
and quality of life, as secondary endpoints.
Patients who participated in the ADMIRAL study and meet study
entry criteria are 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 STK-001. We expect that
LONGWING will also provide valuable information on the preliminary
effects of STK-001 on seizures along with non-seizure aspects of
the disease, such as quality of life and cognition.
Enrollment and dosing in LONGWING are ongoing.
About the BUTTERFLY Observational Study
The BUTTERFLY study is 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 observational 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
by a team of doctors and nurses over time for up to two years. The
study was conducted at approximately 20 sites in the United
States.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company
dedicated to addressing the underlying cause of severe diseases by
upregulating protein expression with RNA-based medicines. 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, 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/ or follow
Stoke on X @StokeTx.
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 STK-001 to treat the underlying causes of
Dravet syndrome and reduce seizures or show improvements in
non-seizure comorbidities at the indicated dosing levels or at all,
and the timing and presentation of data at AES 2023. Statements
including words such as “plan,” “will,” “continue,” “expect,” 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; the timing and results of preclinical and
clinical trials; the risk that 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 and preliminary interim data readouts of ongoing
trials may show results that change when such trials are completed;
the Company’s ability to fund development activities and achieve
development goals; the Company’s ability to protect its
intellectual property; 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, 2022, its quarterly
reports on Form 10-Q, and the other 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231201483257/en/
Stoke Media & Investor Contacts: Dawn Kalmar Chief
Communications Officer dkalmar@stoketherapeutics.com
781-303-8302
Eric Rojas Vice President, Investor Relations
IR@stoketherapeutics.com 617-312-2754
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