– Substantial and durable reductions in
convulsive seizure frequency observed in patients treated with 2 or
3 doses of 70mg followed by 45mg maintenance dosing on top of the
best available anti-seizure medicines –
– Patients experienced continuous improvements
in multiple measures of cognition and behavior with ongoing
treatment through 2 years –
– Data support proposed Phase 3 registrational
study regimen; Update anticipated before year-end –
– Zorevunersen generally well-tolerated across
the studies –
– Data to be presented at the American Epilepsy
Society (AES) 2024 Annual Meeting; Company to host virtual event
for investors and analysts on Monday, December 9 at 8:30 am Eastern
(5:30 am Pacific) –
Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company
dedicated to restoring protein expression by harnessing the body’s
potential with RNA medicine, today announced new data from an
analysis of nine patients treated with an initial 2 or 3 doses of
70mg, followed by 45mg maintenance dosing in the Phase 1/2a and
open-label extension (OLE) studies of zorevunersen. Substantial and
durable reductions in convulsive seizure frequency were observed in
these patients who received zorevunersen on top of the best
available anti-seizure medicines. In addition, patients treated in
the OLE studies showed continuous improvements in multiple measures
of cognition and behavior with ongoing treatment through 2 years.
Zorevunersen was generally well tolerated across the studies.
Together, these data support the company’s proposed Phase 3
registrational study regimen and its efforts to develop
zorevunersen as a disease-modifying medicine for the treatment of
Dravet syndrome.
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20241206101127/en/
Figure 1. Substantial and Durable
Reductions in Convulsive Seizure Frequency from Baseline in
Patients who Received 70mg zorevunersen in Phase 1/2a (Graphic:
Business Wire)
The company will host a virtual educational event for investors
and research analysts on Monday, December 9 at 8:30 am Eastern
(5:30 am Pacific).
“Dravet syndrome is stressful to live with and challenging to
treat. Anti-seizure medicines are helpful in reducing seizures but
can only do so much for patients who continue to experience
significant and life-altering limitations in many aspects of
neurodevelopment and daily living,” 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. “The substantial and durable reductions
in seizures, as well as the continuous gains in multiple measures
of behavior and cognition through 2 years in patients treated in
these studies have never been seen before in studies of Dravet
syndrome. I am encouraged by these data and convinced that we are
on the verge of a new era in the treatment of this disease.”
“The new long-term data give us a more complete and convincing
picture of the potential for zorevunersen as a disease-modifying
medicine,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of
Stoke Therapeutics. “Patients entered our studies with high seizure
rates despite being treated with the best available anti-seizure
medicines. The durability of the substantial reductions in their
seizures, particularly among those treated with initial doses of
70mg are remarkable and support a highly differentiated mechanism
of action for zorevunersen. These data, combined with the
continuous improvements in cognition and behavior, are highly
supportive of our plans to conduct a Phase 3 study and the dose
regimen currently under discussion with global regulatory
agencies.”
Key Study Finding: Substantial and Durable Reductions in
Convulsive Seizure Frequency Poster 2.379 and 2.364
Previously reported end-of-Phase 1/2a study data from patients
treated with two or three doses of 70mg of zorevunersen showed
substantial and sustained reductions in convulsive seizure
frequency of 85% at 3 months (n=10) and 74% at six months (n=9)
post-last dose.
The Company is now reporting data for the nine patients who
continued treatment with at least two doses of 45mg of zorevunersen
in the OLE study. These patients sustained at least a 50% median
reduction from baseline at each month of the OLE and demonstrated
an 87% median reduction at month eight, the latest timepoint for
which data have been assessed for these nine patients. See Figure
1.
Key Study Finding: Continuous Improvements in Multiple
Measures of Cognition and Behavior Patients experienced
continuous improvements in multiple measures of cognition and
behavior as measured by the Vineland-3 through 2 years of treatment
with ongoing maintenance dosing in the OLEs. Additional
improvements were indicated within the first nine months of
treatment among patients in the Phase 1/2a ADMIRAL study. See
Figure 2.
Key Safety Findings At the time of the analysis, 81
patients had been treated with zorevunersen in the Phase 1/2a
studies. Seventy-four patients who completed the Phase 1/2a studies
and were eligible enrolled in the OLEs. As of June 2024, 82%
(61/74) remained in the OLE studies. Safety findings from the
studies are consistent with prior disclosures and are summarized
below.
- Zorevunersen 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. 79% (56/71) 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.
Additional Presentations Small Changes on the
Vineland-3 are Meaningful to Caregivers of Patients with Dravet
Syndrome Poster: 3.383 The Company will also present the
results of a study of caregivers and clinical experts that was
designed to evaluate what constitutes meaningful change on the
Vineland-3 and to generate insight into caregiver perceptions of
the key signs, symptoms and impacts of Dravet syndrome. The study
found that small changes in adaptive behavior, as measured by the
Vineland-3, are considered clinically meaningful by both caregivers
of patients with Dravet syndrome and clinical experts. Changes of 2
to 3 points in growth scale values across subdomains were
considered meaningful by at least 50% of caregivers. Consistent
with other publications, the Expressive Communication and Receptive
Communication subdomains were ranked by caregivers as the most
important areas to improve with treatment. The study further
defines meaningful change thresholds on the Vineland-3 scale to
explore cognitive and behavioral benefits in clinical trials of
potential disease-modifying treatments.
Spectral EEG Analysis Demonstrates Decreased Slow-wave
Activity in Patients with Dravet Syndrome after Treatment with
Zorevunersen, an Antisense Oligonucleotide Poster: 3.407
An EEG analysis of 74 patients treated in clinical studies of
zorevunersen showed a reduction in slow-wave activity following
zorevunersen administration. The treatment effect on spectral power
is most pronounced at the highest zorevunersen doses, with
reductions in slow-wave activity sustained for months after the
last dose. Topographical spectral changes indicate that
zorevunersen produces a widespread and durable effect across the
brain.
All presentations are available for download on the Stoke
Therapeutics website under the Investors & News tab.
Stoke Therapeutics Analyst and Investor Virtual Event
Stoke will host a virtual event with discussions led by leading
clinicians and patient advocates to offer analysts and investors an
opportunity to learn more about Dravet syndrome, its overall
effects, and the potential real-world impacts of a
disease-modifying medicine. As part of this event, the clinicians
are expecting to share anecdotes and visuals from their experience
treating patients in the clinical studies of zorevunersen.
Title: Understanding Dravet Syndrome: The Unmet Need and
Potential for Disease-Modification Date and Time: Monday,
December 9, 8:30-9:30 AM EST (5:30-6:30 AM PST) Presenters:
Edward M. Kaye, M.D., CEO of Stoke Therapeutics, 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; Andreas Brunklaus M.D., Consultant
Paediatric Neurologist at the Royal Hospital for Children, Glasgow,
Honorary Professor at the University of Glasgow, member of Dravet
Syndrome UK's Medical Advisory Board; Mary Anne Meskis, Executive
Director, Dravet Syndrome Foundation; and Veronica Hood, PhD,
Scientific Director, Dravet Syndrome Foundation Webcast
Link: https://edge.media-server.com/mmc/p/bv6h2oxs
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 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. The FDA has
also granted zorevunersen rare pediatric disease designation and
Breakthrough Therapy Designation for the treatment of Dravet
syndrome with a confirmed mutation, not associated with
gain-of-function, in the SCN1A gene.
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 1955, including, but not limited to: the
ability of zorevunersen (STK-001) to treat the underlying causes of
Dravet syndrome and reduce seizures or show improvements in
behavior or cognition at the indicated dosing levels or at all; the
timing and expected progress of clinical trials, data readouts,
regulatory decisions and other presentations for zorevunersen,
including the timing and presentation of data at AES 2024; the
potential for zorevunersen to be the first disease-modifying
therapy for Dravet syndrome; the timing of regulatory interactions
or the outcomes thereof; our expectations, plans, aspirations and
goals, including those related to the potential of zorevunersen.
Statements including words such as "anticipate," "believe," "hope,"
"plan," "will," "continue," expect," "ongoing," or "potential" 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:
our ability to advance, obtain regulatory approval of, and
ultimately commercialize our product candidates, including
zorevunersen; the timing of data readouts and interim and final
results of nonclinical and clinical trials; nonclinical and
clinical data are voluminous and detailed, and regulatory
authorities may interpret or weigh the importance of data
differently and reach different conclusions than us or others,
request additional information, have additional recommendations or
change their guidance or requirements before or after approval;
receiving Breakthrough Therapy Designation may not lead to a faster
development or regulatory review or approval and does not mean
zorevunersen will receive marketing approval; our ability to fund
development activities and achieve development goals; our ability
to protect our intellectual property; 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 our
Annual Report on Form 10-K for the year ended December 31, 2023,
our quarterly reports on Form 10-Q and the other documentation we
file from time to time with the Securities and Exchange Commission.
These forward-looking statements speak only as of the date of this
presentation, and we undertake 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/20241206101127/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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