Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK)
(“Takeda”) and Ovid Therapeutics Inc. (NASDAQ: OVID) (“Ovid”),
a biopharmaceutical company committed to developing medicines that
transform the lives of people with rare neurological diseases,
today announced positive topline results from the randomized Phase
2 ELEKTRA study of soticlestat in children with Dravet syndrome
(DS) or Lennox-Gastaut syndrome (LGS). Soticlestat is a potent,
highly selective, oral, first-in-class inhibitor of the enzyme
cholesterol 24-hydroxylase (CH24H). It is being investigated by
Ovid and Takeda for the treatment of rare developmental and
epileptic encephalopathies (DEEs), a group of highly refractory
epilepsy syndromes including DS and LGS.
The ELEKTRA study achieved its primary endpoint
with high statistical significance, demonstrating a 27.8% median
reduction from baseline in convulsive seizure (DS) and drop seizure
(LGS) frequency compared to a 3.1% median increase in patients
taking placebo during the 12-week maintenance period (median
placebo-adjusted reduction=30.5%; p=0.0007, based on the efficacy
analysis set of 120 patients with seizure data in the maintenance
period). In addition, DS and LGS patients treated with soticlestat
demonstrated a 29.8% median reduction in convulsive seizure (DS)
and drop seizure (LGS) frequency compared to 0.0% change in median
seizure frequency in patients taking placebo during the full
20-week treatment period (titration plus maintenance) of the
ELEKTRA study (placebo-adjusted reduction=25.1%; p=0.0024).
In the ELEKTRA DS cohort (n=51), patients
treated with soticlestat demonstrated a 33.8% median reduction in
convulsive seizure frequency compared to a 7.0% median increase in
patients taking placebo during the full 20-week treatment period of
the study (median placebo-adjusted reduction in seizure frequency
is 46.0%; p=0.0007). Based on these data, the companies plan to
meet with regulatory authorities to discuss initiation of a Phase 3
registrational program for soticlestat in patients with DS.
In the ELEKTRA LGS cohort (n=88), patients
treated with soticlestat demonstrated a 20.6% median reduction in
drop seizure frequency compared to a 6.0.% median reduction in
patients taking placebo during the full 20-week treatment period of
the study (median placebo-adjusted reduction in seizure frequency
is 14.8%; p=0.1279). Additional analyses are being conducted to
better understand the potential next steps for the development of
soticlestat in this highly heterogenous patient population.
Soticlestat was generally well-tolerated in the
ELEKTRA study and demonstrated a safety profile consistent with
those of previous studies, with no new safety signals identified.
All patients who completed the ELEKTRA study elected to enroll into
the ENDYMION open-label extension study and findings from ENDYMION
are also reported today.
“We are extremely encouraged by these results,
which show a clear statistically significant reduction of seizures
in Dravet syndrome patients treated with soticlestat, as well as a
trend for seizure reduction in Lennox-Gastaut patients,” said Amit
Rakhit, M.D., MBA, President and Chief Medical Officer of Ovid. “We
look forward to continuing our collaboration with Takeda to
initiate a Phase 3 registrational program for soticlestat in
patients with DS, while continuing to analyze the data from
patients with LGS in the ELEKTRA and ENDYMION studies to define
potential next steps. We also expect to report data from the
open-label Phase 2 ARCADE study with soticlestat in patients with
CDKL5 deficiency disorder and Dup15q syndrome, two other types of
highly-refractory DEEs, later this quarter.”
“It is exciting to see these positive results
and to advance soticlestat into late stage clinical development --
initially for the potential treatment of children with Dravet
syndrome who need more options to manage treatment-resistant
seizures,” said Sarah Sheikh, M.D., M.Sc., MRCP, Head, Neuroscience
Therapeutic Area Unit at Takeda. “Soticlestat and its novel
mechanism of action were discovered at Takeda and we are
enthusiastic about continuing to advance the science and clinical
programs as one aligned team, in strong partnership with Ovid
Therapeutics.”
“Children with developmental epileptic
encephalopathies like DS and LGS need more options to manage their
treatment-resistant seizures,” said Dr. Cecil Hahn, M.D., MPH, a
Child Neurologist at The Hospital for Sick Children and Associate
Professor of Pediatrics at the University of Toronto. “The results
of the ELEKTRA study are very promising, particularly for
children with DS and represent a clinically significant reduction
in seizure burden. Moreover, soticlestat was well-tolerated in this
study."
Phase 2 ELEKTRA Study Design and Patient
Baseline DemographicsELEKTRA was an international,
multi-center, randomized, double-blind, placebo-controlled study
designed to evaluate treatment with soticlestat in pediatric
patients, aged 2 to 17 years, with highly refractory epileptic
seizures associated with DS (convulsive seizures) or LGS (drop
seizures). The study consisted of a four- to six-week screening
period to establish baseline seizure frequency, followed by a
20-week double-blind treatment period, including an 8-week dose
optimization period and a 12-week maintenance period. During the
8-week dose optimization period, patients were titrated from 100mg
twice daily (BID), to 200mg BID to 300mg BID (mg/kg dosing for
<60 kg) of orally administered soticlestat.
A total of 141 patients were enrolled in ELEKTRA
and 126 completed the study. A modified intent-to-treat (mITT)
analysis of 139 patients was performed to evaluate the efficacy
endpoints, which includes any patient who enrolled in the study and
received at least one dose of study drug. Patients in the study
were allowed to be on one to four concomitant anti-epileptic drugs
(AEDs), with the majority of patients concomitantly treated with at
least three AEDs. The most common AEDs taken by the patients were
valproate, clobazam, levetiracetam and topiramate.
Phase 2 ELEKTRA Topline Efficacy
ResultsThe study achieved its primary endpoint,
demonstrating a 27.8% median reduction from baseline in convulsive
seizure (DS) and drop seizure (LGS) frequency compared to a 3.1%
median increase in patients on placebo during the 12-week
maintenance period (median placebo-adjusted reduction=30.5%;
p=0.0007, based on the efficacy analysis set of 120 patients with
seizure data in the maintenance period). During the full 20-week
treatment period of the mITT DS patient population, the median
percent change from baseline was a 33.8% decrease in seizure
frequency compared to a 7.0% increase in seizure frequency for
patients receiving placebo (median placebo-adjusted
reduction=46.0%; p=0.0007). During the full treatment period of the
mITT LGS patient population, the median percent change from
baseline was a 20.6% decrease in seizure frequency compared to a
6.0% decrease in patients receiving placebo (median
placebo-adjusted reduction=14.8%;
p=0.1279).
Phase 2 ELEKTRA Topline Safety
ResultsSoticlestat was well tolerated in this study. These
findings were consistent with previous studies and no new safety
signals were identified. The incidence of treatment emergent
adverse events was similar in both the treatment and placebo groups
with 57 (80.3%) of soticlestat patients experiencing at least one
treatment emergent adverse event compared to 52 (74.3%) placebo
patients. The most frequent treatment emergent adverse events
reported in soticlestat-treated patients with ≥5% difference from
placebo were lethargy and constipation. The incidence of serious
adverse events was similar in both soticlestat and placebo groups,
with 11 (15.5%) in soticlestat experiencing at least one treatment
emergent serious adverse event compared to 13 (18.6%) in placebo.
There were no deaths reported.
ENDYMION Open-Label Extension Study
UpdateAll patients who completed the ELEKTRA trial elected
to roll over into the ENDYMION open-label extension study. 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.
Data from the ELEKTRA patients who have rolled
over into the ENDYMION study are supportive of results in the core
study. The data indicate maintenance of effect over 6 months in
those patients originally randomized to soticlestat, and similarly
reduced seizure frequency as compared to baseline in those patients
previously assigned to the placebo arm. No new safety signals were
identified in ENDYMION.
About Soticlestat
(TAK-935/OV935)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.
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 Dravet Syndrome and Lennox-Gastaut
SyndromeDravet syndrome and Lennox-Gastaut syndrome are
types of developmental and epileptic encephalopathies (DEEs), a
heterogeneous group of rare epilepsy syndromes. Dravet and
Lennox-Gastaut syndrome typically become apparent during infancy or
early childhood and are highly refractory to many antiseizure
medications.
Dravet syndrome is most commonly caused by a
genetic mutation in the SCN1A gene and affects approximately 1 in
15,000 to 1 in 21,000 people in the United States. Dravet syndrome
is characterized by prolonged focal seizures that can evolve to
convulsive tonic-clonic seizures. Children with Dravet syndrome
experience developmental disabilities as seizures increase. Other
common symptoms include changes in appetite, difficulty balancing
and a crouched gait when walking.
Lennox-Gastaut syndrome is estimated to affect
approximately 1 in 11,000 people in the United States.
Lennox-Gastaut syndrome is a heterogeneous condition and
characterized by several different types of seizures, most commonly
atonic (drop), tonic and atypical absence seizures. Children with
Lennox-Gastaut syndrome may also develop cognitive dysfunction,
delays in reaching developmental milestones and behavioral
problems. Lennox-Gastaut syndrome can be caused by a variety of
underlying conditions, but in some cases no cause can be
identified.
Ovid Conference Call and Webcast
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 7926217. A replay of the webcast will be available on the
Company’s website following the live conference call.
About Takeda Pharmaceutical Company
LimitedTakeda Pharmaceutical Company Limited
(TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven
biopharmaceutical leader headquartered in Japan, committed to
bringing Better Health and a Brighter Future to patients by
translating science into highly-innovative medicines. Takeda
focuses its R&D efforts on four therapeutic areas: Oncology,
Rare Diseases, Neuroscience, and Gastroenterology (GI). We also
make targeted R&D investments in Plasma-Derived Therapies and
Vaccines. We are focusing on developing highly innovative medicines
that contribute to making a difference in people's lives by
advancing the frontier of new treatment options and leveraging our
enhanced collaborative R&D engine and capabilities to create a
robust, modality-diverse pipeline. Our employees are committed to
improving quality of life for patients and to working with our
partners in health care in approximately 80 countries.For more
information, visit https://www.takeda.com.
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assumptions about many important factors, including the following,
which could cause actual results to differ materially from those
expressed or implied by the forward-looking statements: the
economic circumstances surrounding Takeda’s global business,
including general economic conditions in Japan and the United
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of marketed products or product candidates; the impact of health
crises, like the novel coronavirus pandemic, on Takeda and its
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timing and impact of post-merger integration efforts with acquired
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other factors identified in Takeda’s most recent Annual Report on
Form 20-F and Takeda’s other reports filed with the U.S. Securities
and Exchange Commission, available on Takeda’s website at:
https://www.takeda.com/investors/reports/sec-filings/ or at
www.sec.gov. Takeda does not undertake to update any of the
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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
www.ovidrx.com.
Ovid 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 anticipated reporting schedule of clinical data, 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.
Takeda Media Contacts: |
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Japanese MediaKazumi Kobayashikazumi.kobayashi@takeda.com+81 (0)
3-3278-2095 |
Media outside JapanChris Stammchris.stamm@takeda.com+1 (617)
347-7726 |
|
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Ovid Investors and Media: |
|
Ovid Therapeutics Inc.Investor Relations & Public
Relationsirpr@ovidrx.com |
|
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Or |
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Ovid Investors: |
Ovid Media: |
Steve KlassBurns McClellan, Inc.+1 (212)
213-0006sklass@burnsmc.com |
Dan Budwick1ABdan@abmedia.com |
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