- Examination of EEG in healthy subjects administered single
doses of BHV-7000 confirmed central nervous system (CNS) activity
consistent with effects observed with other antiseizure
medications.
- EEG results demonstrated dose-dependent and time-dependent
effects of BHV-7000 on CNS target engagement in study
subjects:
-
- At the lowest dose studied of 10 mg, subjects with targeted
drug concentrations ≥EC50 showed a mean increase in EEG
spectral power in beta and gamma bands while there were no
meaningful changes in spectral power in subjects with drug
concentrations <EC50.
- At the highest dose studied of 50 mg, increases in EEG
spectral power were observed in all frequency bands and across the
entire head without distinct topographies.
- BHV-7000 has been shown to be well tolerated in Phase 1
single ascending dose (SAD) and multiple ascending dose (MAD)
studies to date, with a distinct profile from other Kv7 ion channel
activators and antiseizure medications.
- Biohaven has also successfully completed the development of
an extended-release formulation of BHV-7000 to allow for once-daily
dosing to be studied in future clinical programs.
- With target engagement now confirmed in the biomarker EEG
study, favorable safety profile demonstrated in Phase 1 studies and
development of a once-daily formulation of BHV-7000, Biohaven plans
to initiate its Phase 3 program in focal epilepsy before the end of
2023.
NEW HAVEN, Conn. and
DUBLIN, Ireland,
Sept. 5,
2023 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN)
("Biohaven"), a global clinical-stage biopharmaceutical company
focused on the discovery, development and commercialization of
life-changing therapies to treat a broad range of rare and common
diseases, today announced preliminary analyses and positive
biomarker data from Biohaven's exploratory Phase 1
electroencephalogram (EEG) biomarker study, which was presented to
epilepsy key opinion leaders at an off-site meeting held during the
International Epilepsy Conference 2023 in Dublin, Ireland. The preliminary study results
confirm central nervous system (CNS) activity of BHV-7000 at
projected therapeutic concentrations, dose-dependent and
time-dependent changes in EEG spectral power and are consistent
with EEG effects observed with other antiseizure medications (ASMs)
approved for the treatment of epilepsy. Biohaven's Phase 3 program
in focal epilepsy is anticipated to begin before the end of
2023.
Michael Bozik, M.D., President,
Ion Channel Research & Development at Biohaven, commented "The
EEG biomarker data show effects of BHV-7000 on CNS activity
and are incredibly exciting because they further support the
paradigm-changing potential of our highly selective Kv7.2/7.3
activator. Together with the preclinical data and the favorable
safety and tolerability profile seen in the Phase 1 SAD/MAD
studies, the EEG results highlight BHV-7000's potential to deliver
robust antiseizure efficacy, without the burdensome CNS
adverse effects observed with antiseizure medicines. We are
extremely pleased that the BHV-7000 development program continues
to advance towards our planned Phase 3 start in the fourth quarter
of 2023."
The Phase 1 EEG study was designed to evaluate qualitative
changes from baseline in EEG spectral power after administration of
single doses of BHV-7000 (10, 25, or 50 mg) to healthy volunteers.
EEG spectral power is a measure derived from quantitative analysis
of EEG signals that assesses the amount of rhythmic activity in
different frequency bands, including delta [1-3.5 Hz], theta
[3.5-7.5 Hz], alpha [7.5-13 Hz], beta [13-30 Hz], and gamma [30-100
Hz]. Changes in spectral power have been used to evaluate the risk,
onset and progression of seizures, assess cognitive and behavioral
impairments, and characterize the effects of ASMs; and, they may
also have utility in refining dose selection in clinical trials of
ASMs. Spectral analysis was performed by Epilog (Ghent,
Belgium), a global leader in EEG
analytics.
The Phase 1 EEG study showed dose-dependent and time-dependent
increases in brain spectral power in healthy subjects. At the
lowest dose of 10 mg (n=12), subjects with BHV-7000 concentrations
≥EC50 (based on preclinical maximal electroshock seizure (MES)
models) showed mean increases in EEG spectral power in beta
and gamma bands that were not observed in the group of subjects
with drug concentrations < EC50 [FIGURE 1a and 1b]. These changes in beta and gamma band
activity were consistent with those previously reported for other
ASMs (Biondi et al. 2022). At the highest dose of 50 mg (n=11),
increases in EEG spectral power were observed across all spectral
bands and distributed over all cortical brain regions [FIGURE 2].
In addition to the dose-dependent observations, the time course of
the increase in EEG spectral power in the 50mg dose group
corresponded to the known pharmacokinetic (PK) profile of BHV-7000.
Biohaven expects to present the additional details and analyses
from this EEG study at upcoming scientific meetings.
BHV-7000 was well tolerated in the exploratory EEG study and the
safety profile was consistent with the previously reported safety
data from the Phase 1 SAD/MAD trial completed to date in healthy
volunteers [FIGURE 3]. BHV-7000 has been administered at
single doses of up to 100 mg and multiple doses of up to 80 mg
daily without significant CNS adverse events commonly associated
with other ASMs, including a markedly lower incidence of
somnolence, speech disorder and memory impairment.
Based on the results from the EEG study and preliminary safety
profile in SAD/MAD trials, along with PK data from a new once-daily
extended-release (ER) formulation, Biohaven plans on exploring
three oral doses of BHV-7000 (once daily 25 mg ER, once daily 50 mg
ER, and once daily 75 mg ER) in the Phase 3 focal epilepsy
program. This dosing approach with a Kv7 activator will allow
for assessment of distinct target concentrations over a wide range,
above and below projected efficacious EC50 drug concentrations
[FIGURE 4], not previously feasible with drugs in this class. No
meaningful food effect was observed in the Phase 1 SAD/MAD trial
using BHV-7000 in its standard release formulation.
Vlad Coric, M.D., Chairman and
Chief Executive Officer of Biohaven, commented, "The EEG results
presented are an important milestone after almost a decade of
effort by the ion channel discovery team, led by Drs. Michael Bozik and Steven
Dworetzky, to develop a highly selective Kv7.2/7.3 activator
with a best-in-class drug profile. The EEG data confirms central
nervous system target engagement as measured by dose-dependent
changes in spectral power in expected frequency bands and over the
entire head. These EEG results along with the safety data from the
Phase 1 studies and our formulation group's development of a
once-daily extended-release drug formulation of BHV-7000, allow us
to advance to pivotal trials later this year. We are excited about
evaluating the efficacy of this highly selective Kv7.2/7.3
activator in epilepsy, mood disorders (including bipolar disorder)
and other diseases as the profile of BHV-7000 represents a
potential paradigm shift for this mechanism of action."
About BHV-7000
BHV-7000, the lead asset from
Biohaven's Kv7 platform, is a novel and selective activator of
Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and
in regulating the hyperexcitable state, that Biohaven is developing
for the treatment of epilepsy and mood disorders. BHV-7000 was
rationally developed as a potent activator of heteromeric Kv7.2/7.3
potassium channels, the molecular substrate that underlies the
M-current (IKM). BHV-7000 is highly differentiated from ezogabine
(known as retigabine in Europe), a
Kv7 activator that was previously approved for adjunctive treatment
of partial-onset seizures in adults. In comparison with ezogabine,
BHV-7000 belongs to a significantly different structural class and
differentiates from ezogabine in key properties, including
pharmacology, plasma stability and stability to photooxidation. In
addition, BHV-7000 does not exhibit GABAA receptor
positive allosteric molecular activity as seen with ezogabine and
similar compounds, which may contribute to the poor tolerability of
ezogabine. This lack of GABAA receptor activity
potentially gives BHV-7000 a wide therapeutic window which, based
on dose-dependent clinical responses seen in other ASM clinical
trials, should translate to improved efficacy without the typical
dose dependent side effect profile often seen in patients receiving
ezogabine and other anti-seizure medications.
About Biohaven
Biohaven is a global
clinical-stage biopharmaceutical company focused on the discovery,
development and commercialization of life-changing therapies to
treat a broad range of rare and common
diseases. Biohaven's experienced management team brings
with it a historical track record of delivering new drug approvals
for products for diseases such as migraine, depression, bipolar
disorder and schizophrenia. Biohaven is advancing a pipeline of
therapies for diseases with little or no treatment options,
leveraging its proven drug development capabilities and proprietary
platforms, including Kv7 ion channel modulation for epilepsy and
neuronal hyperexcitability, glutamate modulation for
obsessive-compulsive disorder and spinocerebellar ataxia, myostatin
inhibition for neuromuscular diseases, and brain-penetrant
TYK2/JAK1 inhibition for immune-mediated brain
disorders. Biohaven's portfolio of early- and late-stage
product candidates also includes discovery research programs
focused on TRPM3 channel activation for neuropathic pain, CD-38
antibody recruiting, bispecific molecules for multiple myeloma,
antibody drug conjugates (ADCs), and targeted extracellular protein
degrader platform technology (MoDEs™ platform) with potential
application in neurological disorders, cancer, and autoimmune
diseases. For more information, visit www.biohaven.com.
About Epilog
Epilog is a brand of clouds of care NV,
an ISO 13485:2016 and ISO 27001:2013-certified CNS marketplace.
Epilog's clinical and technical EEG expertise in epileptiform
disorders provides unique EEG-based insights into brain
functioning. With CE-marked and FDA-cleared applications for
clinicians and tailor-made solutions for clinical trials and
research, Epilog is on a mission to optimize epilepsy care as part
of the clouds of care CNS portfolio.
For more information, visit www.epilog.care.
Forward-looking Statements
This news release includes
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. The use of certain words,
including "continue", "plan", "will", "believe", "may", "expect",
"anticipate" and similar expressions, is intended to identify
forward-looking statements. Investors are cautioned that any
forward-looking statements, including statements regarding the
future development, timing and potential marketing approval and
commercialization of development candidates, are not guarantees of
future performance or results and involve substantial risks and
uncertainties. Actual results, developments and events may differ
materially from those in the forward-looking statements as a result
of various factors including: the expected timing, commencement and
outcomes of Biohaven's planned and ongoing clinical trials; the
timing of planned interactions and filings with the Food and Drug
Administration; the timing and outcome of expected regulatory
filings; complying with applicable U.S. regulatory requirements;
the potential commercialization of Biohaven's product candidates;
the potential for Biohaven's product candidates to be best-in-class
or first-in-class therapies; and the effectiveness and safety
of Biohaven's product candidates. Additional important factors
to be considered in connection with forward-looking statements are
described in Biohaven's filings with the Securities and Exchange
Commission, including within the sections titled "Risk Factors" and
"Management's Discussion and Analysis of Financial Condition and
Results of Operations". The forward-looking statements are made as
of the date of this new release, and Biohaven does not undertake
any obligation to update any forward-looking statements, whether as
a result of new information, future events or otherwise, except as
required by law.
MoDEs is a trademark of Biohaven Therapeutics Ltd.
Investor Contact:
Jennifer Porcelli
Vice President, Investor Relations
jennifer.porcelli@biohavenpharma.com
+1 (201) 248-0741
Media Contact:
Mike Beyer
Sam Brown Inc.
mikebeyer@sambrown.com
+1 (312) 961-2502
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