Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical
company committed to developing medicines that transform the lives
of people with rare neurological diseases, today announced results
from the ARCADE and ENDYMION studies of soticlestat (OV935/TAK-935)
in patients with developmental and epileptic encephalopathies
(DEEs), or rare epilepsies. The Phase 2 ARCADE study is a
signal-finding open-label pilot study of soticlestat in patients
with CDKL5 deficiency disorder (CDD) and Dup15q syndrome (Dup15q),
two highly refractory rare epilepsies that have no approved
treatment options, while ENDYMION is an open-label long-term
extension study with soticlestat. All patients who completed the
ARCADE study opted to roll over into ENDYMION. Soticlestat is a
potent, highly selective, oral, first-in-class inhibitor of the
enzyme cholesterol 24-hydroxylase (CH24H) being developed in
collaboration with Takeda Pharmaceutical Company Limited.
Together, data from the ARCADE and ENDYMION studies show seizure
frequency reduction over time. In CDD patients (n=12), median motor
seizure frequency reduction was 24% during the 12-week maintenance
period in the ARCADE study, increasing to a 50% reduction in the
ENDYMION long-term extension study in the five CDD patients who
reached nine months of continuous treatment. In Dup15q patients
(n=8), there was an increase in median motor seizure frequency in
the ARCADE study during the 12-week maintenance period; however,
longer-term data from the four Dup15q patients who reached nine
months of continuous treatment showed a 74% reduction in median
motor seizure frequency. Soticlestat was generally well tolerated
in both studies and continues to demonstrate a favorable safety
profile. Data reported today are consistent with, and build upon,
previous findings with soticlestat.
“CDD and Dup15q patients have various seizure types and are on
multiple concomitant antiseizure medications per current medical
practice, and yet they still lack significant control of their
respective seizures,” said Amit Rakhit, M.D., MBA, President and
Chief Medical Officer of Ovid Therapeutics. “Data from ARCADE,
while a small open-label study, and ENDYMION support previous
findings of the early activity of soticlestat and, importantly, the
longer-term ENDYMION study shows seizure frequency reduction across
multiple rare epilepsies over time. Data from ARCADE and ENDYMION
will help inform next development steps for the soticlestat program
in CDD and Dup15q, while we prepare to discuss data from our Phase
2 ELEKTRA study in Dravet syndrome and Lennox-Gastaut syndrome with
the FDA.”
“Anti-epileptic drugs can lose efficacy over time. Soticlestat
may produce acute and long-term antiseizure effects in addition to
potential improvements outside of motor seizure frequency reduction
as suggested by clinical global impression scales,” said Scott
Demarest, M.D., child epileptologist, Assistant Professor of
Pediatrics and Neurology at the University of Colorado.
“Soticlestat is emerging as a potentially valuable therapeutic
option, particularly given its favorable safety profile and
potential to provide a durable treatment benefit. Patients with
these disorders need more options to manage their
treatment-resistant seizures, and collective data from the Phase 2
ELEKTRA, ARCADE and ENDYMION studies warrant further investigation
of soticlestat.”
ARCADE is a Phase 2 open-label, signal-finding pilot study
designed to inform the potential for future development of
soticlestat in CDD and Dup15q. The study enrolled 20 patients, ages
2 to 55 years, with refractory epileptic seizures associated with
CDD (n=12) or Dup15q (n=8) and consisted of a four- to six-week
screening period to establish baseline seizure frequency, followed
by a 20-week treatment period, including an eight-week
titration/dose optimization period and a 12-week maintenance
period. Patients in the study were allowed to be on one to six
concomitant anti-epileptic drugs (AEDs), with the majority of
patients concomitantly treated with at least four AEDs,
representing a highly refractory patient population. The primary
objective of the ARCADE study was to determine percent change from
baseline in motor seizure frequency during the 12-week maintenance
period. Afterward, patients were offered the chance to continue
soticlestat treatment in the ENDYMION open-label extension study,
and all patients who completed ARCADE elected to roll over into
ENDYMION.
ENDYMION is a multi-center, open-label extension study of
soticlestat in any patient who has participated in any previous
soticlestat DEE clinical study, including patients with CDD,
Dup15q, Dravet syndrome and Lennox-Gastaut syndrome. The primary
objective of ENDYMION is to assess the long-term safety and
tolerability of soticlestat in patients with DEEs and, secondarily,
to evaluate the effect of soticlestat on seizure control over
time.
Data from CDKL5 Deficiency Disorder
(CDD)CDD patients exhibited a variety of seizures types,
including motor (tonic and atonic) and cluster seizures, as well as
epileptic spasms. In CDD patients (n=12), median motor seizure
frequency reduction was 14% during the 20-week study period
(eight-week dose titration and 12-week maintenance period) and 24%
during the 12-week maintenance period (primary objective of the
study). In the ARCADE study, two CDD patients experienced a ≥50% to
<75% reduction in motor seizures, and one CDD patient
experienced a ≥75% reduction in motor seizures during the 20-week
study period. All CDD patients rolled over into the ENDYMION
open-label extension study and continue to receive soticlestat.
Five CDD patients have reached nine months of continuous treatment
with soticlestat, achieving a 50% median motor seizure frequency
reduction at this time interval. Beyond motor seizures, individual
CDD patients also demonstrated improvements in other seizure types,
as reported previously.
Overall clinical benefit of treatment was assessed by the
Clinical Global Impression of Change (CGI-C; investigator) and
Caregiver Global Impression of Change (Care GI-C) scales. 67% of
CDD patients were deemed markedly improved with minimal or no
adverse events on the CGI-C scale after starting soticlestat
treatment. For the Care-GI-C scale, 92% of caregivers reported
improvement on soticlestat treatment at the end of the ARCADE
study, with 42% reporting much and very much improved. In the
ARCADE study CDD cohort, exit interviews from the caregiver also
give insight into improvements in verbal and nonverbal
communication, alertness/level of engagement, overall quality of
daily functioning and caregiver-chosen domains to suggest benefits
of soticlestat treatment in domains beyond seizure control.
Data from
Dup15q
SyndromeDup15q patients also exhibited a variety
of seizures types, including motor (tonic and atonic), myoclonic
and absence seizures. In Dup15q patients (n=8), there was an
increase in median motor seizure frequency of 13% during the
20-week study period (eight-week dose titration and 12-week
maintenance period) and an increase of 12% during the 12-week
maintenance period (primary objective of the study). However,
longer-term data from the four Dup15q patients who reached nine
months of continuous treatment with soticlestat in ENDYMION showed
a 74% reduction in median motor seizure frequency. Individual Dup15
patients demonstrated improvements in other seizure types, as
reported previously.
In addition, 38% of Dup15q patients were deemed markedly
improved with minimal or no adverse events on the CGI-C scale after
starting soticlestat treatment. For the Care-GI-C scale, 50% (in
4/8 patients) of caregivers reported improvement on soticlestat
treatment at the end of the ARCADE study. Exit interviews from the
caregiver for the ARCADE study Dup15 cohort also show similar
improvements to the CDD patients in the study.
Safety and Tolerability
Profile of
SoticlestatSoticlestat was
generally well tolerated in the ARCADE study and demonstrated a
safety profile consistent with the findings of previous studies
with no new safety signals identified. The most common adverse
events were constipation (n=4/20, 20%), rash (n=3/20, 15%) and
seizure (n=3/20, 15%). Additionally, there were no serious adverse
events considered related to study drug or deaths reported. As with
the initial ARCADE data, longer-term results from the ARCADE
patients who enrolled in ENDYMION continue to demonstrate a safety
profile consistent with previous findings.
In the ARCADE study, a reduction of plasma 24HC levels was
observed with soticlestat treatment, and plasma 24HC continues to
show potential as a biomarker of pharmacodynamic activity.
Detailed efficacy and safety data is included in the Company’s
updated corporate presentation, which can be accessed via the
presentations and events section of Ovid’s website.
About Soticlestat
(OV935/TAK-935)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.
Ovid and Takeda recently announced positive topline results from
the randomized Phase 2 ELEKTRA study of soticlestat in children
with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS).
Takeda and Ovid are sharing in the development and
commercialization costs of soticlestat on a 50/50 basis, and if
successful, the companies will share in the profits on a 50/50
basis. Takeda will be responsible for commercialization in Japan
and has the option to be responsible for commercialization in other
countries in Asia and other selected countries. Ovid will be
responsible for clinical development activities and
commercialization of soticlestat in the United States, Europe,
Canada and Israel. Under the terms of the agreement, Takeda
received equity in Ovid and may be eligible to receive certain
milestone payments based on the advancement of soticlestat.
About CDKL5 Deficiency Disorder and Dup15q
SyndromeCyclin-dependent kinase-like 5 (CDKL5) deficiency
disorder (CDD) and Duplication 15q (Dup15q) syndrome are rare and
severe developmental and epileptic encephalopathies (DEEs) caused
by genetic mutations 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
(DEEs)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 DEEs 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 Ovid TherapeuticsOvid 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 (DEEs). For more information on Ovid,
please visit www.ovidrx.com.
Forward-Looking StatementsThis
press release includes certain disclosures that contain
“forward-looking statements,” including, without limitation,
statements regarding the potential benefits, clinical and
regulatory development and commercialization of soticlestat, the
potential value and benefits of the collaboration with Takeda, the
likelihood that data will support future development, and the
association of data with treatment outcomes. You can identify
forward-looking statements because they contain words such as
“will,” “appears,” “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 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.” Such risks may be amplified by
the COVID-19 pandemic and its potential impact on Ovid’s business
and the global economy. 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:Dan Budwick1ABdan@1abmedia.com
Ovid Therapeutics (NASDAQ:OVID)
Historical Stock Chart
From Aug 2024 to Sep 2024
Ovid Therapeutics (NASDAQ:OVID)
Historical Stock Chart
From Sep 2023 to Sep 2024