NEW YORK & OSAKA, Japan-Thursday 27 August 2020 [ AETOS Wire ]
− Primary
endpoint achieved, demonstrating a statistically significant reduction
of seizures from baseline compared to placebo (p=0.0007) in the combined
Dravet syndrome and Lennox-Gastaut syndrome study population
− Statistically
significant reduction in seizure frequency from baseline in Dravet
syndrome cohort compared to placebo (p=0.0007); based on strong efficacy
results, Takeda and Ovid plan to initiate a Phase 3 registrational
program of soticlestat in Dravet syndrome
− Data
from Lennox-Gastaut syndrome cohort demonstrated numeric reductions in
seizure frequency compared to placebo but did not achieve statistical
significance (p=0.1279); data analysis ongoing for the Lennox-Gastaut
syndrome patients
− Soticlestat
was well-tolerated and demonstrated a safety profile consistent with
the findings of previous studies with no new safety signals identified
− Ovid to host conference call and webcast today at 8:00 a.m. EDT
(BUSINESS WIRE) -- 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 Demographics
ELEKTRA
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 administered="" kg="" of="" orally="" soticlestat.="" span="">
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 Results
The
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 Results
Soticlestat
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 Update
All
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 Syndrome
Dravet
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 Information
Ovid
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 Limited
Takeda 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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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 www.ovidrx.com.
Ovid Forward-Looking Statements
This
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.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200825005303/en/Contacts
Takeda Media:
Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81 (0) 3-3278-2095
Media outside Japan
Chris Stamm
chris.stamm@takeda.com
+1 (617) 347-7726
Ovid Investors and Media:
Ovid Therapeutics Inc.
Investor Relations & Public Relations
irpr@ovidrx.com
Or
Ovid Investors:
Steve Klass
Burns McClellan, Inc.
+1 (212) 213-0006
sklass@burnsmc.com
Ovid Media:
Dan Budwick
1AB
dan@abmedia.com
