Ovid Therapeutics Inc. (NASDAQ: OVID) today announced positive
initial data from the ENDYMION trial, a Phase 2 open-label
extension study of soticlestat (OV935/TAK935) in patients with rare
developmental and epileptic encephalopathies (DEE). DEE is a
heterogeneous group of rare highly-refractory epilepsy syndromes
and encompasses Dravet syndrome, Lennox-Gastaut syndrome (LGS), and
others. Soticlestat is a potent, highly-selective first-in-class
inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H) being
investigated as a novel approach to treating adults and children
with rare epilepsies in collaboration with Takeda Pharmaceutical
Company Limited.
This initial data from the ENDYMION open-label extension trial
is from patients who previously completed Ovid’s 12-week Phase
1b/2a clinical trial of soticlestat in adults with DEE. At 12
weeks, safety and tolerability observations with soticlestat in the
ENDYMION study were consistent with the completed Phase 1b/2a
clinical trial. Furthermore, longer-term data from ENDYMION out to
48 weeks suggest increased seizure reduction with prolonged
treatment of soticlestat in this difficult-to-treat, adult patient
population with various types of DEE. Median seizure frequency
reductions were 84% following 25-36 weeks (n=6) and 90% following
37-48 weeks (n=4) of treatment. In addition, the longest
seizure-free durations experienced by two different patients were
264 consecutive days and 150 consecutive days, respectively.
“While this first data cut includes a small number of patients,
these initial results from ENDYMION reaffirm the potential of
soticlestat to provide a tangible and durable clinical benefit for
patients with DEE, a group of difficult-to-treat seizure disorders
with limited therapeutic options,” said Amit Rakhit, MD, MBA, Chief
Medical Officer and Head of Research & Development at Ovid.
“Specifically, we believe the sustained and progressively-improving
median seizure reduction up to 90% seen in these patients is
encouraging and, while early, compares favorably to other studies
in different types of DEE. We look forward to additional progress
in our broad DEE clinical development program including initial
data from the ARCADE study expected in Q1 2020 and topline results
from the randomized ELEKTRA study now expected in 2H 2020 as a
result of robust enrollment.”
ENDYMION Study Design ENDYMION is a
prospective, multi-center, open-label extension study of
soticlestat in patients with DEE who have participated in a
previous soticlestat clinical study. The primary objective of
ENDYMION is to assess the long-term safety and tolerability of
soticlestat over two years of treatment in patients with rare
epilepsies and secondarily, to evaluate the effect of soticlestat
on seizure frequency over time.
Upon completion of a previous soticlestat clinical study,
patients have the option to enroll in the open-label ENDYMION study
with titration up to maintenance dose. Target dosing is 600mg per
day (300mg twice a day) for adults and weight-based dosing for
pediatric patients. Based on the insights gained from the previous
12-week Phase 1b/2a clinical trial of soticlestat in adults with
DEE and, as previously announced, Ovid amended the ENDYMION study
protocol to prohibit perampanel as a concomitant medication due to
a potential interaction.
Patient Baseline DemographicsENDYMION initially
enrolled 7 patients who previously completed the 12-week Phase
1b/2a clinical trial of soticlestat in adults with DEE. Patients
entering the trial experienced multiple seizure types, including
motor seizures. Patients were on a number of anti-epileptic
medications. The patient population was highly-heterogeneous and
was not enriched for any specific condition and patients were each
diagnosed with one of multiple DEEs. One patient enrolled into
ENDYMION prior to the completion of the Phase 1b/2a clinical trial
and was on concomitant perampanel. This patient was withdrawn from
ENDYMION and data is not reported for this patient. Thus, the
primary analysis reported today consists of 6 patients.
These 6 patients were re-baselined for seizure frequency due to
a lag period ranging from 6 to 52 weeks between their completion of
the Phase 1b/2a adult DEE study and the initiation of the ENDYMION
study.
Seizure Frequency Reduction ResultsOverall,
findings suggest that prolonged treatment with soticlestat leads to
increased seizure frequency reduction and is consistent with the
believed mechanism of action of soticlestat.
Table 1: % Reduction from Baseline in Seizure Frequency
|
Weeks 1-12(n=6) |
Weeks 13-24(n=6) |
Weeks 25-36(n=6) |
Weeks 37-48(n=4)* |
Overall median % reduction in seizure frequency from baseline |
48% |
65% |
84% |
90% |
% of patients with ≥50% reduction in seizure frequency from
baseline |
50% |
50% |
67% |
75% |
*two patients have not yet completed 48 weeks of dosing |
Patient baseline seizure frequency ranged from 2 to 71
(median=11.5). In general, a greater reduction in seizure frequency
was observed in those with higher baseline seizure frequency. In
terms of overall seizure free interval during treatment, one
patient experienced 264 consecutive days and one patient
experienced 150 consecutive days without a seizure.
In addition to the 6 patients from the Phase 1b/2a adult DEE
study included in this data analysis, all patients who have
completed the ARCADE and ELEKTRA studies to date have rolled over
into ENDYMION. Data from patients who have completed the ARCADE
study are not included in today’s analysis due to their limited
treatment duration in the ENDYMION study. Data from patients
previously treated in the ELEKTRA study are not included in today’s
analysis due to the ongoing study being double-blinded and
placebo-controlled. Ovid looks forward to reporting initial data
from the ARCADE trial in Q1 2020 as previously guided. As a result
of robust enrollment, Ovid now expects to report topline results
from the ELEKTRA trial in 2H 2020.
SafetyOverall, safety findings are consistent
with prior observations in the 12-week Phase 1b/2a adult DEE study.
Soticlestat continues to show a favorable safety and tolerability
profile. The majority of adverse events (AEs) were mild and
comparable with those from the Phase 1b/2a adult DEE study.
Specifically, AE’s that occurred included upper abdominal pain,
pyrexia, bronchial wall thickening, and rales. There was one
treatment-related AE of nausea. No serious adverse events (SAEs)
were observed.
About the Ongoing ARCADE and ELEKTRA Trials
Beyond the ENDYMION open-label extension study, Ovid and Takeda are
also conducting the Phase 2 ARCADE and ELEKTRA trials in pediatric
DEE patient populations. Upon the completion of the ARCADE and
ELEKTRA trials, patients are eligible to enroll in the ENDYMION
open-label extension study.
ARCADE is a Phase 2, multi-center, open-label, pilot study that
will evaluate the treatment of soticlestat in approximately 30
patients, aged 2 to 35 years old, with refractory epileptic
seizures associated with CDKL5 Deficiency Disorder (CDD) or Dup15q
syndrome. This study consists of a four to six-week screening
period to establish baseline seizure frequency followed by a
20-week treatment period. The primary endpoint is the change in
motor seizure frequency in patients treated with soticlestat by
disorder. Initial data is expected in Q1 2020.
ELEKTRA is an international Phase 2, multi-center, randomized,
double-blind, placebo-controlled study that will evaluate the
treatment of soticlestat in approximately 126 pediatric patients,
aged 2 to 17 years, with epileptic seizures associated with Dravet
syndrome or Lennox-Gastaut syndrome (LGS). The study consists of a
four to six-week screening period to establish baseline seizure
frequency followed by a 20-week treatment period. The primary
endpoint is the change from baseline in seizure frequency in
patients treated with soticlestat compared to placebo by disorder.
Topline results are expected in 2H 2020.
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 Soticlestat Soticlestat (OV935/TAK-935)
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 potentiates 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 AED. The United
States Food and Drug Administration (FDA) has granted orphan drug
designation to soticlestat for the treatment of both Dravet
syndrome and Lennox-Gastaut syndrome (LGS). Soticlestat is an
investigational drug, not approved for commercial use.
About the Ovid/Takeda Collaboration Ovid and
Takeda entered into a global development and commercialization
collaboration in January 2017 to evaluate soticlestat across a
range of rare epilepsy syndromes. Under the terms of the agreement,
the companies share in the development and commercialization costs
on a 50/50 basis and, if successful, the companies will share in
the profits on a 50/50 basis. Takeda will lead commercialization in
Japan and has the option to lead in Asia and other selected
geographies. Ovid leads clinical development activities and will
lead commercialization in the United States, Europe, Canada and
Israel.
Conference Call InformationOvid Therapeutics
will host a live conference call and webcast today at 8:00 a.m.
Eastern Time. The live webcast can be accessed by visiting the
Investors section of the company’s website at investors.ovidrx.com.
Alternatively, please call 866-830-1640 (U.S.) or 210-874-7820
(international) to listen to the live conference call. The
conference ID number for the live call is 5709139. A replay of the
webcast will be available on the company’s website for two weeks
following the live conference call.
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 (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 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 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 Engleman 1AB katie@1abmedia.com
(919) 333-7722
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