Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company
committed to developing medicines that transform the lives of
people with rare neurological diseases, today announced initial
data from its ongoing exploratory Phase 2 open-label ARCADE study
of soticlestat (OV935/TAK935) in patients with CDKL5 deficiency
disorder (CDD) and Dup15q syndrome (Dup15q). CDD and Dup15q are two
rare, highly refractory developmental and epileptic
encephalopathies (DEE) that have no approved treatment options.
These early data demonstrate that soticlestat, a potent, highly
selective, first-in-class inhibitor of the enzyme cholesterol
24-hydroxylase (CH24H), shows a reduction in seizure frequency
compared to baseline levels in individual patients.
“This initial data set from the open-label ARCADE
study includes the first 11 patients enrolled. This data cut was
designed to confirm the safety profile of soticlestat in these
patient populations and assess any signals of efficacy. These
initial data suggest that soticlestat continues to be safe and well
tolerated and appears to reduce seizure frequency in a majority of
the individual patients,” said Amit Rakhit, M.D., MBA, President
and Chief Medical Officer of Ovid Therapeutics. “These early
results are encouraging and are supportive of continuation of the
ARCADE study. We are also encouraged that all ARCADE patients that
have completed the study to date have opted to roll over into the
ENDYMION open-label extension study. We will work closely to
evaluate the full data from the ARCADE study, expected in the first
quarter of 2021.”
Matthew During, M.D., D.Sc., Chairman of the
Company’s Scientific Advisory Board and Visiting Professor of
Translational Neuroscience, University of Oxford, commented, “While
this initial data includes only a limited number of patients, these
results of the ARCADE open-label trial are encouraging
and support the safety and tolerability of soticlestat in CDD and
Dup15q. More data is needed to assess efficacy, but initial data
support the potential of soticlestat to provide a clinical benefit
for patients with these ultra-rare and treatment-refractory
epilepsy disorders. These initial results support continued
recruitment and enrollment into the study.”
Phase 2 ARCADE Study Design and Patient
Baseline Demographics
ARCADE is an ongoing, multicenter, open-label,
pilot study of soticlestat in patients ages 2 to 55 with refractory
epileptic seizures associated with CDD or Dup15q and will enroll up
to 30 patients. This study consists of a four- to six-week
screening period to establish baseline seizure frequency followed
by an eight-week dose optimization period and a 12-week maintenance
period. Afterward, patients are offered the chance to continue in
Ovid’s open-label extension trial (ENDYMION).
The preliminary data reported today includes a
total of 11 patients, five with CDD and six with Dup15q. In the CDD
cohort, the median age was 4 years and baseline overall seizure
frequency ranged from 10 to 326 per 28 days. In the Dup15q cohort,
the median age was 13.5 years and baseline overall seizure
frequency ranged from 35 to 630 per 28 days. The majority of these
patients were concomitantly treated with at least two
anti-epileptic drugs (AEDs). The most common AEDs taken by the
patients were topiramate, clobazam, felbamate, rufinamide and
valproate.
Phase 2 ARCADE Study – Initial Efficacy
Data
Due to the limited number of patients in this
initial data cut, Ovid will provide the median seizure reduction
and other endpoints with the full data release expected in the
first quarter of 2021. Data from the first 11 patients suggests
that soticlestat may reduce seizure frequency compared to baseline
levels in individual patients.
In the CDD cohort (n=5), patients exhibited a
variety of seizures types including motor (tonic and atonic) and
cluster seizures, as well as epileptic spasms.
- One patient showed an improvement of 61% fewer motor seizures
during the maintenance phase (75% reduction during the full
treatment period) with two consecutive seizure-free 28-day
intervals.
- A second patient showed similar improvement with 63% motor
seizure reduction during the maintenance phase (30% reduction over
the full treatment period).
- A third patient with cluster seizures had a 45% reduction
during the maintenance phase (47% reduction over the full treatment
period).
- Three patients with epileptic spasms (including two of the
three mentioned above) had a 21%, 95% and 100% reduction during the
maintenance phase and (29%, 98% and 90% reduction in spasms
respectively over the full treatment period).
- One of the five patients did not show a meaningful improvement
in any type of seizure reduction. Of interest, this patient had
poor treatment compliance (40% compared to an average of 96% for
the other ten patients in both cohorts).
- In the three patients that completed the full treatment period
at the time of this data cut, motor seizure-free days in two of
these patients increased by 37% and 38%, the third patient did not
show improvement.
In the Dup15q cohort (n=6), patients also exhibited
a variety of seizures types including motor (tonic and atonic),
myoclonic and absence seizures.
- In one patient with pure motor seizures (34.8 seizures per
28-day baseline), seizure frequency was reduced by 90% during the
12-week maintenance phase (89% over the full treatment period).
This patient also had two 28-day seizure-free periods.
- The other five patients in the Dup15q cohort with mixed seizure
types showed preliminary signs of efficacy, as follows:
° Three patients with myoclonic
seizures showed a 60%, 66% and 100% reduction over the maintenance
period (and by 74%, 65% and 100% respectively over the full
treatment period).° Two patients had absence seizures and
showed a 78% and 74% reduction in absence seizures during the
maintenance phase (74% and 51% reduction over the full treatment
period).
- In the five patients that completed the full treatment period
at the time of this data cut, motor seizure free days in four of
these patients increased by 64%, 159%, 539% and 590%, the fifth
patient did not show improvement.
Phase 2 ARCADE Study – Initial Safety
Results
Soticlestat was generally well-tolerated in this
study and demonstrated a safety profile consistent with the
findings of previous studies. The most common adverse events were
constipation (n=3; 27%), fatigue (n=2; 18%), nasopharyngitis (n=2;
18%) and seizure (n=2; 18%). Additionally, there were no adverse
event-related withdrawals, serious adverse events or deaths
reported.
Initial Long-Term Open-Label Extension Data
from ARCADE Patients Rolling Over into ENDYMION
All patients that have completed the ARCADE study
have enrolled in ENYDMION. The primary objective of ENDYMION is to
assess the long-term safety and tolerability of soticlestat over
four years of treatment in patients with rare epilepsies and
secondarily, to evaluate the effect of soticlestat on seizure
frequency over time.
As with the initial ARCADE data, longer-term
results from the patients who enrolled in ENDYMION continue to
demonstrate a safety profile consistent with previous findings.
There was no treatment interruption prior to rollover into ENDYMION
and the baseline seizure frequency used in the analysis below is
the ARCADE baseline. Six patients from the ARCADE study completed
at least 12 weeks of treatment in ENDYMION. Seizure reduction data
from this cohort further supports the potential of soticlestat in
these highly refractory conditions.
- In the CDD cohort (n=2) one patient had a reduction in overall
seizures of 56% during their most recent 12-week interval (24
weeks).
- In the Dup15q cohort (n=4) all four patients had a reduction in
overall seizures. Two patients had a reduction of 24% and 96%
during their first 12-week interval. The other two patients had a
reduction of 50% and 61% during their most recent 12-week interval
(48 weeks).
- One CDD patient did not improve.
About CDKL5 Deficiency Disorder and Dup15q
Syndrome
Cyclin-dependent kinase-like 5 (CDKL5) deficiency
disorder (CDD) and Duplication 15q (Dup15q) syndrome are rare and
severe developmental and epileptic encephalopathies (DEE) caused by
genetic mutation in the CDKL5 gene on the X chromosome and partial
duplication of Chromosome 15, respectively. These mutations are
thought (among other effects) to result in excess transmission of
glutamate, an excitatory neurotransmitter, that in turn leads to
epilepsy and other characteristic neurobehavioral symptoms of CDD
and Dup15q syndrome. Despite the availability of medicines for
epilepsy generally, there are no approved therapies for CDD and
Dup15q syndrome.
About Developmental and Epileptic
Encephalopathies (DEE)
The International League Against Epilepsy (ILAE)
defines an epileptic encephalopathy as a condition in which "the
epileptiform EEG abnormalities themselves are believed to
contribute to a progressive disturbance in cerebral function."
These epilepsies cause significant morbidities for patients beyond
what might be expected from the known underlying pathology alone
and can worsen over time. Developmental and epileptic
encephalopathies typically present early in life and are often
associated with severe cognitive and developmental impairment in
addition to frequent treatment-resistant seizures throughout the
person's lifetime. These disorders vary in age of onset,
developmental outcomes, etiologies, neuropsychological deficits,
electroencephalographic (EEG) patterns, seizure types, and
prognosis.
Despite the availability of medicines for epilepsy,
there are few approved therapies for DEE and for several types
there are no approved therapies. Novel therapies are needed as
current therapies fail to alter the course of the disease or
address co-morbidities, and many patients suffer from resistant
seizures despite treatment with multiple anti-epileptic drugs
(AEDs).
About OV935/TAK935
(soticlestat)
Soticlestat is a potent, highly selective,
first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase
(CH24H), with the potential to reduce seizure susceptibility and
improve seizure control. CH24H is predominantly expressed in the
brain, where it converts cholesterol into 24S-hydroxycholesterol
(24HC) to adjust the homeostatic balance of brain cholesterol. 24HC
is a positive allosteric modulator of the NMDA receptor and
modulates glutamatergic signaling associated with epilepsy.
Glutamate is one of the main neurotransmitters in the brain and has
been shown to play a role in the initiation and spread of seizure
activity. Recent literature indicates that CH24H is involved in
over-activation of the glutamatergic pathway through modulation of
the NMDA channel and that increased expression of CH24H can disrupt
the reuptake of glutamate by astrocytes, resulting in
epileptogenesis and neurotoxicity. Inhibition of CH24H by
soticlestat reduces the neuronal levels of 24HC and may improve
excitatory/inhibitory balance of NMDA channel activity. To Ovid’s
knowledge, soticlestat is the only molecule with this mechanism of
action in clinical development as an anti-epileptic drug (AED).
Ovid and Takeda are conducting a comprehensive
Phase 2 clinical development program with soticlestat in people
with Developmental and Epileptic Encephalopathies (DEE), a
heterogeneous group of rare highly refractory epilepsy syndromes
that encompasses Dravet syndrome, Lennox-Gastaut syndrome and
others. The FDA has granted orphan drug designation to soticlestat
for the treatment of both Dravet syndrome and Lennox-Gastaut
syndrome.
About Ovid Therapeutics
Ovid Therapeutics Inc. is a New York-based
biopharmaceutical company using its BoldMedicine® approach to
develop medicines that transform the lives of patients with rare
neurological disorders. Ovid has a broad pipeline of potential
first-in-class medicines. The company’s most advanced
investigational medicine, OV101 (gaboxadol), is currently in
clinical development for the treatment of Angelman syndrome and
Fragile X syndrome. Ovid is also developing OV935 (soticlestat) in
collaboration with Takeda Pharmaceutical Company Limited for the
potential treatment of rare developmental and epileptic
encephalopathies (DEE). For more information on Ovid, please visit
http://www.ovidrx.com/.
Forward-Looking Statements
This press release includes certain disclosures
that contain “forward-looking statements,” including, without
limitation, statements regarding: advancing and commercializing
Ovid’s product candidates, progress, timing, scope and the
potential therapeutic benefits based on results of clinical trials
for Ovid’s product candidates; and the anticipated reporting
schedule of clinical data regarding Ovid’s product candidates. You
can identify forward-looking statements because they contain words
such as “will,” “believes” and “expects.” Forward-looking
statements are based on Ovid’s current expectations and
assumptions. Because forward-looking statements relate to the
future, they are subject to inherent uncertainties, risks and
changes in circumstances that may differ materially from those
contemplated by the forward-looking statements, which are neither
statements of historical fact nor guarantees or assurances of
future performance. Important factors that could cause actual
results to differ materially from those in the forward-looking
statements include uncertainties related to the global COVID-19
pandemic, uncertainties in the development and regulatory approval
processes, and the fact that initial data from clinical trials may
not be indicative, and are not guarantees, of the final results of
the clinical trials and are subject to the risk that one or more of
the clinical outcomes may materially change as patient enrollment
continues and/or more patient data become available. Additional
risks that could cause actual results to differ materially from
those in the forward-looking statements are set forth in Ovid’s
filings with the Securities and Exchange Commission under the
caption “Risk Factors”. Ovid assumes no obligation to update any
forward-looking statements contained herein to reflect any change
in expectations, even as new information becomes available.
Contacts
Investors and Media:Ovid Therapeutics Inc.Investor
Relations & Public Relationsirpr@ovidrx.com
Or
Investors:Steve KlassBurns McClellan,
Inc.sklass@burnsmc.com(212) 213-0006
Media:Katie Engleman1ABkatie@1abmedia.com(919)
333-7722
Ovid Therapeutics (NASDAQ:OVID)
Historical Stock Chart
From Mar 2024 to Apr 2024
Ovid Therapeutics (NASDAQ:OVID)
Historical Stock Chart
From Apr 2023 to Apr 2024