- Phase 1 Clinical Trials of TAK-935/OV935
Demonstrated a Strong Safety Profile and Well Characterized
Pharmacokinetic Profile, Supporting Further Clinical Advancement
-
Ovid Therapeutics Inc. (NASDAQ:OVID), a biopharmaceutical
company committed to developing medicines for patients with rare
neurological diseases, today announced results appearing in five
poster presentations, including two Phase 1 clinical trials, two
preclinical studies and a dosing model, supporting the clinical
advancement of TAK-935/OV935 as a potential treatment for
developmental and epileptic encephalopathies. The data were
presented at the American Epilepsy Society 71st Annual Meeting,
taking place December 1-5, 2017, at the Walter E. Washington
Convention Center in Washington, D.C.
In January 2017, Takeda and Ovid Therapeutics formed a global
collaboration focused on the clinical development and
commercialization of TAK-935/OV935, a potent and highly selective
cholesterol 24-hydroxylase (CH24H) inhibitor being investigated in
adults with developmental and epileptic encephalopathies. These
results are the first TAK-935/OV935 data to be presented by Takeda
and Ovid Therapeutics.
“We are pleased with the results of these studies, which
validate CH24H inhibition as a novel target for epilepsy treatment
and also form a strong foundation supporting our ongoing clinical
development and biomarker strategy for TAK-935/OV935,” said Dr.
Emiliangelo Ratti, head of Takeda’s Central Nervous System
Therapeutic Area Unit. “Not only do these results reinforce the
safety and tolerability of this potential therapy, but they also
provide vital information for the design and dosing of future
clinical trials.”
TAK-935/OV935 was investigated in healthy subjects in two
randomized, double-blind, placebo controlled Phase 1 clinical
trials, including a single ascending dose study and a multiple
ascending dose study. Results demonstrated that TAK-935/OV935 had a
generally favorable safety profile and was well tolerated up to a
dose of 1,350 mg in the single ascending dose study and at once
daily doses up to 400 mg in the multiple ascending dose study.
Additionally, a clinical trial simulation was conducted using the
results from four Phase 1 clinical trials to create a population
pharmacokinetic (PK) model. Together with the results from
preclinical studies that demonstrated a correlation between
systemic TAK-935/OV935 exposure and reduction in brain 24HC levels,
this model can be used to guide dosing in future trials of
TAK-935/OV935.
“These results support our broader development strategy for
TAK-935/OV935, which includes development in younger patient
populations since developmental and epileptic encephalopathies are
often diagnosed early in life. We believe providing an early
intervention may alter the course of the disease,” said Amit
Rakhit, M.D., MBA, chief medical and portfolio management officer
of Ovid Therapeutics. “We are excited about these data and the
potential of TAK-935/OV935 to be an impactful treatment for people
with developmental and epileptic encephalopathies who currently do
not have sufficient therapeutic options. We are looking forward to
the results of our ongoing Phase 1b/2a clinical trial of
TAK-935/OV935 in adults with developmental and epileptic
encephalopathies, which are expected in 2018.”
As part of Takeda and Ovid’s development strategy, plasma 24HC
is being assessed as a potential biomarker for TAK-935/OV935. The
results of clinical and preclinical studies demonstrate that there
is a dose-dependent correlation between TAK-935/OV935 treatment and
reduction of plasma 24HC levels. This may support the use of plasma
24HC concentration as a biomarker that can inform the design of
future clinical trials and help clinicians individualize the dosing
of TAK-935/OV935.
The poster presentations are listed below. The full abstracts
can be found at: https://www.aesnet.org/annual_meeting/
- Clinical Trial Simulations Using a
Pharmacokinetic/Enzyme Occupancy/Pharmacodynamic Model of TAK-935,
a Cholesterol 24S-hydroxylase Inhibitor (#344434) -
The model-based approach allowed integration of pertinent PK and
pharmacodynamic data to select a dose and a regimen that optimize
response while ensuring an acceptable safety and tolerability
profile in pediatric patients.
- Safety, Tolerability, Pharmacokinetics and
Pharmacodynamics of Single Ascending Doses of TAK-935 in Healthy
Subjects (#344521) - In a Phase 1, randomized,
double-blind, placebo-controlled study, single ascending oral doses
of up to 1,350 mg of TAK-935/OV935 or placebo were administered to
48 healthy subjects under fasted conditions. - TAK-935/OV935
was shown to have an acceptable safety profile and was well
tolerated following a single administration up to 1,350 mg.
- Safety, Tolerability, Pharmacokinetics and
Pharmacodynamics of Multiple Ascending Doses of TAK-935 in Healthy
Subjects (#344533) - In a Phase 1, randomized,
double-blind, placebo-controlled study, 40 healthy subjects
received ascending oral doses of TAK-935/OV935 (100, 300, 400 or
600 mg once daily or 300 mg twice daily) for 14 days. -
TAK-935/OV935 had an acceptable safety profile and was well
tolerated following once-daily doses of up to 400 mg for 14 days in
healthy subjects. Plasma 24HC concentrations decreased by 47 to 63
percent from baseline in a dose-dependent fashion and achieved
steady state levels by day 7.
- Evaluation of Pharmacodynamic Effects of Cholesterol
24-hydroxylase Inhibitor TAK-935 and Its Target Engagement in
Animals (#344659) - Reduction in 24HC levels was
highly correlated with TAK-935/OV935 systemic exposures in rodents.
- Inhibition of Cholesterol 24-hydroxylase is a Novel
Pharmacological Strategy for Epilepsy Treatment
(#344660) - In the preclinical model, TAK-935/OV935
delayed the onset of seizure development, indicating that an
approximate 50 percent reduction in brain 24HC levels can produce a
therapeutic benefit.
About Developmental and Epileptic
EncephalopathiesThe term epileptic encephalopathy includes
a group of epilepsy syndromes associated with severe cognitive and
behavioral disturbances. 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.
Examples of this category of epilepsy includes the following
epilepsy syndromes:
- Early myoclonic encephalopathy (EME)
- Early infantile epileptic encephalopathy (EIEE/Ohtahara
syndrome)
- Infantile Spasm (West Syndrome)
- Dravet syndrome (severe myoclonic epilepsy in infancy;
SMEI)
- Malignant epilepsy with migrating partial seizures in
infancy
- Doose syndrome (myoclonic astatic epilepsy)
- Myoclonic status in nonprogressive encephalopathies
- Lennox-Gastaut syndrome (LGS)
- Landau-Kleffner syndrome (LKS)
- Epilepsy with continuous spike-waves during slow sleep
(CSWS)
- Rasmussen's encephalitis
Despite the availability of medicines for epilepsy, few
treatment options are available for epileptic encephalopathies, and
novel therapies are needed.
About TAK-935/OV935TAK-935/OV935, which is
being studied in developmental and epileptic encephalopathies, is a
potent, highly-selective, first-in-class inhibitor of the enzyme
cholesterol 24-hydroxylase (CH24H). CH24H is predominantly
expressed in the brain, where it plays a central role in
cholesterol homeostasis. CH24H converts cholesterol to 24HC, which
then exits the brain into the blood plasma circulation. 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 CH24H is involved in
over-activation of the glutamatergic pathway through modulation of
the NMDA channel, implying its potential role in central nervous
system diseases such as epilepsy. To Ovid’s knowledge,
TAK-935/OV935 is the only molecule with this mechanism of action in
clinical development.
TAK-935/OV935 has been tested in preclinical models to provide
data to support the advancement of the drug into human clinical
studies in patients suffering from rare epilepsy syndromes. A novel
proprietary PET ligand, developed by Takeda and Molecular
Neuroimaging, LLC (MNI), has been used to determine target
occupancy of TAK-935/OV935 in the brain. In addition, the effect of
TAK-935/OV935 on CH24H enzyme activity in the brain has been
assessed by following measurable reductions in the plasma
concentration of 24HC.
TAK-935/OV935 has completed four Phase 1 clinical studies, which
have assessed tolerability and target engagement at doses believed
to be therapeutically relevant. TAK-935/OV935 is being co-developed
by Ovid and Takeda Pharmaceutical Company Limited.
About Ovid TherapeuticsOvid Therapeutics
(NASDAQ:OVID) is a New York-based biopharmaceutical company using
its BoldMedicine™ approach to develop therapies that transform the
lives of patients with rare neurological disorders. Ovid’s drug
candidate, OV101, is currently in development for the treatment of
Angelman syndrome and Fragile X syndrome. Ovid initiated the Phase
2 STARS trial of OV101 in people with Angelman syndrome in 2017 and
completed a Phase 1 trial in adolescents with Angelman syndrome or
Fragile X syndrome. Ovid is also developing OV935 in collaboration
with Takeda Pharmaceutical Company Limited for the treatment of
epileptic encephalopathies and in August 2017 initiated a Phase
1b/2a trial of OV935.
For more information on Ovid, please visit
http://www.ovidrx.com/.
Forward-Looking StatementsThis press release
includes certain disclosures that contain
“forward-looking statements,” including, without limitation,
statements regarding progress, timing, scope and results of
clinical trials for Ovid’s product candidates, the development of
therapies for younger patients, the provision of access to
effective therapies, and the execution of Ovid goals for not only
OV101 but also OV935, and the use of plasma concentration 24HC
concentration as a biomarker to inform future clinical trial
designs and to help clinicians individualize the dosing of
TAK-935/OV935. 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 are set forth in Ovid’s filings with the Securities and
Exchange Commission, including its Quarterly Report on Form
10-Q for the quarter ended September 30, 2017, 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.
ContactsInvestors: Burns McClellan Steve Klass,
212-213-0006 Sklass@burnsmc.com
Media: Pure Communications, Inc. Katie Engleman, 910-509-3977
katie@purecommunicationsinc.com
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