– Phase 1/2a End of Study Data: 70mg doses
demonstrated substantial and sustained reductions in convulsive
seizure frequency on top of the best available anti-seizure
medicines; Median reductions of 85% (n=10) at 3 months and 74%
(n=9) at 6 months after last dose –
– Open Label Extension Studies: Durable
reductions in seizures and clinically meaningful improvements in
multiple measures of cognition and behavior were maintained over 12
months with continued dosing at 30mg and 45mg –
– STK-001 generally well-tolerated –
– Company to meet with regulatory agencies to
discuss registrational study design with initial doses of 70mg
followed by continued dosing at 45mg –
– Webcast and conference call for analysts and
investors at 4:30 p.m. Eastern Time today –
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 landmark new data from two open-label Phase 1/2a studies
and two open-label extension (OLE) studies of children and
adolescents ages 2 to 18 with Dravet syndrome who were treated with
STK-001. Data from these studies showed clinically meaningful
effects, including substantial and durable reductions in convulsive
seizure frequency and improvements in multiple measures of
cognition and behavior that support the potential for disease
modification. These improvements were observed among a highly
refractory group of patients who were already taking the best
available anti-seizure medicines. STK-001 has been generally
well-tolerated in studies to date.
Today, the Company also announced clearance from the U.S. Food
and Drug Administration (FDA) that allows patients to receive three
doses of 70mg followed by continued dosing at 45mg. Based on this
regulatory update and these data, the Company plans to meet with
regulatory agencies to discuss a registrational study that includes
initial doses of 70mg followed by continued dosing at 45mg.
“The totality of these data provide compelling evidence that
support the potential for STK-001 to be a disease-modifying
medicine for patients with Dravet syndrome by treating the
underlying cause of the disease, rather than just the symptoms,”
said Edward M. Kaye, M.D., Chief Executive Officer of Stoke
Therapeutics. “STK-001 is the first medicine in development to
demonstrate substantial and durable reductions in seizure frequency
and improvements in multiple measures of cognition and behavior.
These effects were observed in patients who were already taking the
best available anti-seizure medicines, which confirms our highly
differentiated mechanism of action and approach to treating this
disease. We look forward to meeting with regulatory agencies to
discuss our plans for a randomized, controlled registrational study
and to providing an update coming out of those discussions later in
2024.”
“For decades, the primary goal of treating Dravet syndrome has
been to control the frequency and severity of seizures, but, as we
can now see from natural history data, many patients still
experience high rates of seizure frequency and fall further and
further behind in their neurodevelopment,” 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. “A 50% reduction in seizures is an important measure of
clinical efficacy, so an 80% reduction on top of any benefit
patients may already be getting from their baseline anti-seizure
regimen is profound. The further evidence of improvements in skills
like communication, behavior, socialization and movement
distinguish this approach from anything we have seen to date and
mark our entry into a new era in the treatment of Dravet
syndrome.”
Phase 1/2a Study Results: Substantial and Sustained
Reductions in Convulsive Seizure Frequency
The Phase 1/2a studies were multi-center and included children
and adolescents who have an established diagnosis of Dravet
syndrome. Patients enrolled in these studies were highly refractory
to treatment and taking the best available anti-seizure medicines:
85% of patients were taking at least three and 54% were taking at
least four medicines to control seizures. Half the patients in the
studies were taking concomitant fenfluramine.
New data from a combined analysis of 19 clinically evaluable
patients who were treated with one, two or three doses of 70mg
demonstrated substantial reductions in convulsive seizure frequency
compared to baseline at 3 months and at 6 months after the last
dose, one of several secondary endpoints in each study.
Observed Reductions in Convulsive Seizure Frequency Among
Patients Treated with 70mg Doses of STK-001 in the Phase 1/2a
Studies
Median % Reduction from Baseline
in Convulsive Seizure Frequency
70mg
(1 dose, n=8)
70mg
(2 or 3 doses, n=11)
At 3 Months After Last Dose
43% (n=8)
85% (n=10†)
At 6 Months After Last Dose
57% (n=7*)
74% (n=9†)
*Seizure data excluded from month 5-6 for 1 patient because
>50% seizure diary was missing †Seizure data excluded for 2
patients (1 patient prior to 3m after last dose, 1 prior to 6m
after last dose) following a change in background anti-seizure
medicines
Open Label Extension Studies: Durable reductions in seizures
and clinically meaningful improvements in multiple measures of
cognition and behavior over 12 months with continued dosing at 30mg
and 45mg
Eligible patients who completed treatment in the Phase 1/2a
studies continued treatment with STK-001 in one of two OLEs. At the
time of the analysis, 92% (68/74) of eligible patients had enrolled
in the OLEs and 84% (57/68) remained in the studies.
Durable reductions in convulsive seizure frequency were observed
throughout the course of treatment. This analysis only included
patients who received >30mg of
STK-001 in the Phase 1/2a studies and then continued treatment with
STK-001 (30mg or 45mg) every four months in the OLEs. Clinically
meaningful improvements from baseline through 12 months were
observed in multiple measures of cognition and behavior, including
multiple sub-domains of the Vineland Adaptive Behavior Scale
(VINELAND-3).
These improvements are in stark contrast to recent natural
history study data that showed that, on average, patients with
Dravet syndrome 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.
Key Safety Findings
At the time of the analyses, 81 patients had been treated with
STK-001. Safety findings are summarized below.
- STK-001 was generally well-tolerated across the Phase 1/2a and
OLE studies.
- In the Phase 1/2a studies:
- 30% (24/81) of patients experienced a treatment-emergent
adverse event (TEAE) that was related to study drug. The most
common were CSF protein elevations and procedural vomiting;
and
- 22% (18/81) of patients had a treatment-emergent serious
adverse event. These events were assessed as unrelated to study
drug except for the previously reported case of one patient who
experienced Suspected Unexpected Serious Adverse Reactions
(SUSARs).
- A greater incidence of CSF protein elevation was observed in
the OLEs. 74% (50/68) of patients in the OLEs had at least 1 CSF
protein value >50 mg/dL. No clinical manifestations have been
observed in these patients.
- Across the studies, one patient discontinued treatment due to
study drug. As previously reported, this patient discontinued
treatment in the OLE due to elevated CSF protein.
Stoke Webcast and Conference Call for Analysts and
Investors
Stoke will host a webcast and conference call for analysts and
investors at 4:30 p.m. Eastern Time on March 25, 2024, to present
landmark new data from two Phase 1/2a studies and two ongoing
open-label extension (OLE) studies in children and adolescents ages
2 to 18 with Dravet syndrome. The webcast will be broadcast live on
the Investors & News section of Stoke’s website at
https://investor.stoketherapeutics.com/. Participants who want to
join the call and ask a question may register here to receive the
dial-in numbers and unique PIN to seamlessly access the call.
Otherwise please access the listen-only webcast by clicking here.
An archived replay of the webcast will be available for at least 90
days following the event.
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 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 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 STK-001. The study is
also evaluating the long-term effects of STK-001 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 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 STK-001 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 STK-001. The study is
also evaluating the long-term effects of STK-001 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 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 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/.
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
behavior and cognition at the indicated dosing levels or at all,
and the timing and expected progress of clinical trials, data
readouts, regulatory meetings, regulatory decisions and other
presentations. 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 STK-001; 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 into 2025; 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240325745654/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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