NEW HAVEN, Conn., June 24, 2020 /PRNewswire/ -- Biohaven
Pharmaceutical Holding Company Ltd. (NYSE: BHVN) today reported
topline results from its proof of concept study of troriluzole in
the treatment of obsessive-compulsive disorder (OCD).
Table 1 shows the mean change in the Yale-Brown
Obsessive-Compulsive Scale (Y-BOCS) total score over time.
Troriluzole treated subjects had a mean Y-BOCS improvement of -5.1
points from baseline versus -3.6 for placebo-treated subjects
[difference -1.5, p-value=0.041, 95% CI: -3.02, -0.06] at week 8,
and -5.9 points versus -4.9 for placebo subjects [difference -1.0,
p-value = 0.220, 95% CI: -2.59, 0.60] at week 12. Although the
p-value in this proof of concept study did not reach statistical
significance at the primary Y-BOCS
endpoint at week 12, the results reveal a consistent treatment
benefit of troriluzole over time and provide the appropriate data
to power future studies.
Table 1:
Troriluzole Effect on OCD in Phase 2/3
Trial1
|
Y-BOCS Total
Change from
Baseline
|
Week
|
4 (N=115a,
111b)
|
8 (N=108a,
96b)
|
12 (N=102a,
99b)
|
Placeboa
|
-2.9
|
-3.6
|
-4.9
|
Troriluzoleb
|
-3.4
|
-5.1*
|
-5.9
|
p-value
|
0.451
|
0.041
|
0.220
|
1. BHV4157-202 Final
Unblinded Analysis YBOCS Total Change from Baseline by Week
LSMeans from MMRM Model MITT Data Set
|
* p < 0.05 versus
placebo
|
Troriluzole treatment differences compared to placebo were
greater in patients who were more severely ill at baseline (i.e.,
Y-BOCs total scores greater than the median score of 26,
representing severe OCD symptoms), see Table 2. Troriluzole treated
subjects (n=42) had a mean Y-BOCS change from baseline of -6.0
points versus -3.1 for placebo (n=45) subjects [difference -2.9,
p=0.035, 95% CI: -5.49, -0.21] at week 8, and -7.0 points (n=44)
versus -4.6 for placebo (n=43) subjects [treatment difference -2.4,
p = 0.084, 95% CI: -5.18, 0.33] at week 12.
Table 2:
Troriluzole Effect on Patients with Severe
OCD1
|
Y-BOCS Total
Change from
Baseline
|
Week
|
4 (N=47a,
49b)
|
8 (N=45a,
42b)
|
12 (N=43a,
44b)
|
Placeboa
|
-3.5
|
-3.1
|
-4.6
|
Troriluzoleb
|
-4.1
|
-6.0*
|
-7.0
|
p-value
|
0.584
|
0.035
|
0.084
|
1. Patients at
baseline with median Y-BOCS total scores > 26 (severe OCD
symptoms).
|
* p < 0.05 versus
placebo
|
|
|
Vlad Coric, M.D., Chief Executive
Officer of Biohaven, "While we have focused our primary investment
to date on our lead CGRP program for migraine, we advanced
troriluzole in a series of proof of concept trials to assess signal
detection across disease states. Our strategy is to only
further invest in troriluzole indications where we find an emerging
drug signal. We are pleased to report these OCD study results
that show a consistent and clinically meaningful drug effect at all
study timepoints in patients who had an inadequate response to
existing standard of care treatments. This study provides our
R&D team with the necessary data to refine and adequately power
subsequent trials to advance troriluzole in OCD. Based upon these
results, we will have an End of Phase 2 meeting with the FDA and
plan to initiate an appropriately powered pivotal Phase 3 study of
two doses of troriluzole versus placebo."
Obsessive-compulsive disorder is a serious psychiatric condition
affecting over 2 million individuals in the U.S. and significantly
impacts quality of life. Approximately 40% to 60% of OCD patients
continue to experience significant residual symptoms despite
approved therapies. Some refractory patients undergo psychosurgery
(cingulotomy or deep brain stimulation) to alleviate their
crippling symptoms.
Dr. Christopher Pittenger, M.D.,
Ph.D., Associate Professor of Psychiatry and Director of the Yale
OCD Research Clinic, who was an investigator in the trial,
commented, "As the first large scale, double-blind trial of
troriluzole in OCD, this proof-of-concept study provides extremely
encouraging initial data. OCD affects one person in 40 and
can be debilitating. Fully a third of patients do not respond to
current treatments, and many who do respond continue to suffer from
residual symptoms. New therapies are urgently needed to
alleviate this suffering and disability. There has not been a
mechanistically novel medication approved for OCD in over 20
years. If troriluzole proves to be effective for these
patients, it would be a huge advance. I look forward to
working with Biohaven to explore the data from this
proof-of-concept trial in more depth, to inform the design of
future pivotal studies."
Loren Aguiar, M.D., Biohaven's
Vice President of Research and Development stated, "The team
conducted a well-designed, comprehensive proof of concept trial
which has provided a wealth of data about the use of troriluzole as
adjunctive therapy in OCD. We are continuing to analyze these
data to investigate additional factors that may inform our next
studies and further minimize placebo effect. The completion of the
trial was complicated by the presence of restrictions surrounding
the COVID-19 pandemic. We are grateful to the community of patients
and researchers who persevered, allowing us to undertake and
complete this challenging study."
Biohaven has a deep and broad portfolio of assets in development
with five ongoing Phase 3 trials across its calcitonin gene-related
peptide (CGRP) antagonists, glutamate modulators and
myeloperoxidase inhibitor platforms. Biohaven continues to focus
resources on the NURTEC ODT launch for the acute treatment of
migraine in adults, while preparing an sNDA submission for
prevention. Earlier this year, troriluzole dosed at 280 mg
successfully advanced past an interim futility analysis, performed
after 100 subjects completed 6 months of treatment, in its pivotal
Phase 2/3 trial in Alzheimer's disease. Completion of the
trial for troriluzole in Alzheimer's Disease trial is expected in
4Q2020, and topline data from the troriluzole in SCA trial are
anticipated in 2021. Additionally, Biohaven's verdiperstat trial in
Multiple System Atrophy (MSA) is enrolling ahead of schedule with
topline results also expected in 2021.
About Troriluzole
Troriluzole is a third-generation
prodrug and new chemical entity that modulates glutamate, the most
abundant excitatory neurotransmitter in the human body. The primary
mode of action of troriluzole is normalization of synaptic levels
of glutamate. Troriluzole increases glutamate uptake from the
peri-synaptic space, by augmenting the expression and function of
excitatory amino acid transporters (i.e., EAAT2 also called GLT-1)
located on glial cells that play a key role in clearing glutamate
from the synapse. More information about troriluzole can be found
on the Company's website
https://www.biohavenpharma.com/science-pipeline/glutamate/troriluzole
About Biohaven
Biohaven is a biopharmaceutical company
focused on the development and commercialization of innovative
best-in-class therapies to improve the lives of patients with
debilitating neurological and neuropsychiatric diseases. Biohaven's
neuroinnovation portfolio includes FDA-approved NURTECâ„¢ ODT
(rimegepant) for the acute treatment of migraine and a broad
pipeline of late-stage product candidates across three distinct
mechanistic platforms: CGRP receptor antagonism for the acute and
preventive treatment of migraine; glutamate modulation for
obsessive-compulsive disorder, Alzheimer's disease, and
spinocerebellar ataxia; and myeloperoxidase (MPO) inhibition for
multiple system atrophy and amyotrophic lateral sclerosis. For more
information, visit www.biohavenpharma.com.
Forward-Looking Statements
This news release includes
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. These forward-looking
statements involve substantial risks and uncertainties, including
statements that are based on the current expectations and
assumptions of Biohaven's management. All statements, other than
statements of historical facts, included in this press release,
including the expected enrollment for Biohaven's Phase 2b/3 trial of troriluzole, the potential results
of Biohaven's Phase 2b/3 trial of
troriluzole in OCD, the potential for the Phase 2b/3 trial to be a pivotal trial, the role of
glutamate in OCD, the possible benefits of troriluzole as
adjunctive therapy compared to current standard of care for OCD
patients, as well as the timetable for the topline data and
completion of trials, are forward-looking statements. The use of
certain words, including the "believe" and "will" and similar
expressions are intended to identify forward-looking statements.
Biohaven may not actually achieve the plans and objectives
disclosed in the forward-looking statements and you should not
place undue reliance on Biohaven's forward-looking statements.
Various important factors could cause actual results or events to
differ materially from those that may be expressed or implied by
our forward-looking statements, including uncertainties relating to
the future clinical success of troriluzole. Additional important
factors to be considered in connection with forward-looking
statements are described in the "Risk Factors" section of
Biohaven's Annual Report on Form 10-K filed with the Securities and
Exchange Commission on February 26,
2020 and Biohaven's Quarterly Report on Form 10-Q for the
quarter ended March 31, 2020, filed
with the Securities and Exchange Commission on May 7, 2020. The forward-looking statements are
made as of this date 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.
For further information, contact:
Dr. Vlad Coric
Chief Executive Officer
Vlad.Coric@biohavenpharma.com
NURTEC is a trademark of Biohaven Pharmaceutical Holding Company
Ltd.
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SOURCE Biohaven Pharmaceutical Holding Company Ltd.