- Biohaven reported full results from the BHV-7000 Phase 1 study
examining doses up to 120 mg daily, demonstrating BHV-7000 was
well-tolerated at all doses studied without the typical central
nervous system (CNS) adverse effects associated with other
anti-seizure medications (ASMs), such as somnolence and
cognitive/mood disturbances.
- In a Phase 1 electroencephalogram (EEG) biomarker study,
BHV-7000 demonstrated dose-dependent target engagement in the brain
as measured by changes in EEG spectral power across all brain
regions.
- Additional poster presentations at the American Epilepsy
Society Annual Meeting will include: BHV-7000 preclinical data,
health-related quality of life in patients with focal epilepsy, and
functional impairments in patients with KCNQ2‐associated
developmental and epileptic encephalopathy (KCNQ2-DEE).
NEW
HAVEN, Conn., Dec. 1, 2023
/PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) announced today
that it is presenting expanded EEG and safety data for BHV-7000 at
the 2023 American Epilepsy Society (AES) Annual Meeting, taking
place December 1-5, 2023, in
Orlando, Florida. The
presentations include results from the BHV-7000 Phase 1 EEG
biomarker study and additional BHV-7000 safety and tolerability
data from Phase 1 single ascending dose (SAD) / multiple ascending
dose (MAD) studies. Additional posters showcase BHV-7000's
preclinical data, findings from a systematic literature review on
health-related quality of life (HRQoL) in patients with focal
epilepsy, and results from a cross-sectional survey assessing
functional impairments in patients with KCNQ2-DEE.
Jason Lerner, M.D., Medical
Director and Epilepsy Clinical Lead at Biohaven, commented
"Selective Kv7 activators are one of the most exciting new drug
targets for the treatment of epilepsy, and BHV-7000 has shown a
favorable and differentiated profile in preliminary Phase 1 studies
to date. We are pleased to see favorable safety and tolerability
with BHV-7000 dosed up to 120 mg daily for 15 days, without the CNS
adverse effects typically associated with other ASMs, such as
somnolence. Together with the preclinical data showing BHV-7000 is
a selective Kv7.2/7.3 channel opener lacking GABAA
activation and the results from our Phase 1 EEG study confirming
target engagement, we are excited to advance BHV-7000 into
late-stage development in epilepsy patients."
Dr. Lerner added, "The robust BHV-7000 data presentations at the
AES meeting underscore Biohaven's progress and commitment to
developing novel, efficacious and well-tolerated therapies for
people living with epilepsy."
In addition, both the systematic literature review and parental
survey illustrated the importance of Health-Related Quality of Life
issues among patients with focal epilepsy and developmental
manifestations of KCNQ2-DEE that are relevant to parents, such as
communication, eating abilities, and motor impairments.
Presentation Highlights:
Poster 2.510: Novel, Selective Kv7.2/7.3 Potassium Channel
Activator, BHV-7000, Demonstrates Dose-Dependent Pharmacodynamic
Effects on EEG Parameters in Healthy Adults
- In this Phase 1 study, pharmacodynamic activity of BHV-7000 in
the brain of healthy adults was demonstrated by dose-dependent
increases in EEG spectral power.
- Unlike prior reports where EEG effects of a Kv7.2/7.3 activator
showed the greatest power increase in the delta frequency band
(Biondi et al. 2022), the highest spectral power increases with
BHV-7000 were seen in alpha, beta, and gamma frequency bands.
- While changes in spectral power were observed across all
frequency bands with BHV-7000, the minimal impact on slower
frequencies (i.e., delta) is consistent with the low incidence of
CNS adverse events, in particular somnolence, seen in the BHV-7000
Phase 1 SAD/MAD studies.
- EEG delta activity is associated with somnolence, an
undesirable CNS adverse event often seen with other ASMs.
Poster 3.265: A First in Human Phase 1 Study Evaluating the
Safety and Tolerability of BHV-7000, a Novel, Selective Kv7.2/7.3
Potassium Channel Activator, in Healthy Adults
- BHV-7000 was safe and well-tolerated at single doses up to 100
mg and multiple doses up to 120 mg daily for 15 days
- No serious adverse events or severe treatment emergent adverse
events were reported
- Adverse events typically associated with other ASMs, such as
somnolence and cognitive/mood disturbances, were not reported
Poster 2.249: Characterization of BHV-7000: A Novel Kv7.2/7.3
Activator for the Treatment of Seizures
- BHV-7000 is a potent activator of Kv7.2/7.3 channels, impacting
both deactivation kinetics and voltage dependence of
activation
- BHV-7000 requires the Kv7.2 W236 residue for channel
activity
- No significant activation of the GABAA receptor with
BHV-7000
- BHV-7000 is potent in the maximal electroshock seizure (MES)
test without impact on neurobehavior or motor (rotorod)
behavior
Poster 1.487: Determinants of Health-Related Quality of Life
of Patients with Focal Epilepsy: A Systematic Literature
Review
- This systematic literature review identified multiple factors
associated with lower HRQoL in patients with focal epilepsy
- Depression and anxiety were among the most significant and
frequent determinants of HRQoL change
- Other relevant and frequent determinants of HRQoL change
included cognition, ASM adverse events, seizure freedom, and
employment
- A comprehensive understanding of the modifiable determinants of
HRQoL is relevant to patient health and well-being and can inform
clinical practice and observational/interventional studies
Poster 2.451: Functional Impairments in Patients with
KCNQ2-DEE: Associations Among Key Clinical Features
- Data obtained from a cross-sectional survey (2018-2020) of
parents of children aged ≥2 years with KCNQ2-DEE was analyzed
- Among individuals with KCNQ2-DEE, there is a hierarchy of
impairments wherein communication is the most sensitive domain and
is often affected in isolation from others
- Gross and fine motor skill impairments tend to be
correlated
- Hand use impairment is closely correlated with multiple other
functional impairments
Full posters will be available on the Posters and
Presentations page at: www.biohaven.com.
Reference
Biondi A, et al. Sci Rep. 2022 Feb 4;12(1):1919.
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 track record of delivering new drug approvals for
products for diseases such as migraine, depression, bipolar and
schizophrenia. The company is advancing a pipeline of therapies for
diseases, many of which have limited 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 metabolic disorders, and
brain-penetrant TYK2/JAK1 inhibition for neuroinflammatory
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
degradation platform technology (MoDE™) with potential application
in neurological disorders, cancer, and autoimmune diseases.
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 FDA; 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 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 news
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
201-248-0741
Media Contact:
Mike
Beyer
Sam Brown Inc.
mikebeyer@sambrown.com
312-961-2502
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