NEW HAVEN, Conn., April 9, 2020 /PRNewswire/ -- Biohaven
Pharmaceutical Holding Company Ltd. (NYSE: BHVN) ("Biohaven") today
announced that it submitted Pre-IND/IND material to the
U.S. Food and Drug Administration (FDA) to initiate a Phase 2
study of vazegepant, an intranasal, high-affinity calcitonin
gene-related peptide (CGRP) receptor antagonist, for the treatment
of COVID-19 infection associated pulmonary complications. The IND
was approved by the Division of Pulmonary, Allergy, and Critical
Care at FDA on April 8th
and Biohaven was informed that the study may proceed
immediately. Vazegepant is currently advancing to Phase 3
development for the acute treatment of migraine in adults under the
Division of Neurology, having recently reported a successful end of
Phase 2 clinical and nonclinical interaction with FDA.
Vlad Coric, M.D., Chief Executive
Officer of Biohaven commented, "Given the unprecedented global
threat to life that COVID-19 infection represents, there is an
urgent need to test novel approaches to mitigating the consequences
of the infection, including reducing the hyper-immune reaction that
drives much of the morbidity and mortality in the pulmonary effects
of this viral disease." Dr. Coric added, "This pandemic is a call
to action for our entire industry. I am grateful to our
collaborators at the pulmonary institute at Thomas Jefferson and the team at Biohaven that
moved so quickly to develop a clinical protocol and submit this IND
to the FDA in the weeks after the pandemic first developed.
We owe a debt of gratitude to the scientists at the NIH, FDA,
academic centers and pharmaceutical companies who are working hard
to study therapies that might battle this terrible disease -- the
innovative efforts of the true unsung scientific heroes of this
crisis will only be fully recognized once better treatments are
developed to treat COVID-19."
Jesse Roman, M.D., Professor,
Jane & Leonard Korman Respiratory Institute - Jefferson Health
and National Jewish Health, Thomas Jefferson
University, and co-Principal Investigator in the proposed
COVID-19 study commented, "Hospitals and our health care
system are being overwhelmed by those patients who are progressing
to serious COVID-19 infection. There is an urgent need to identify
treatments that can mitigate the inflammatory process in these
patients and help stabilize our response to the pandemic. It's
critical that we move quickly to test immune-modulating drugs like
vazegepant and other agents as to assess if they can provide some
benefit."
Biohaven's proposed clinical study of vazegepant is a Phase 2
double blind, randomized, placebo-controlled, safety and efficacy
trial of intranasal vazegepant for COVID-19 infected hospitalized
patients requiring supplemental oxygen. Data from the proposed
study will allow characterization of the relative safety and
efficacy of intranasal vazegpant versus placebo in the treatment of
COVID-19 leading to hospitalization and the primary outcome
measures will include pulmonary resolution of symptoms, or
progression to ventilator support or death. The study will be
overseen at Biohaven by Steven
Schnittman, M.D., a seasoned infectious disease clinical
researcher and pharmaceutical drug developer. Michael Baram, M.D., Thomas
Jefferson University, Pulmonary Critical Care and Emergency
Medicine, will be the Principal Investigator for the study.
Donnie McGrath, M.D., Chief of
Corporate Strategy of Biohaven commented, "There is a solid
scientific rationale supporting testing of small molecule
CGRP-antagonists as a way to mitigate the neuro-immune consequences
of respiratory viral infections like COVID-19. While the biology is
complex and CGRP has pleotropic effects on the immune system, CGRP
release as a result of viral activation of TRP channels is
implicated in COVID-19 features such as cough, fever and pain, and
the subsequent release of interleukin 6 (IL-6). IL-6 is an
important mediator of inflammation that is elevated in the sickest
of COVID-19 patients. In addition, CGRP may be involved in the
polarization of the T cell response in some COVID-19 patients
towards the pro-inflammatory state characterized by Th17 and IL-17
(see Figure)."
Acute lung injury is known to induce upregulation of transient
receptor potential (TRP) channels which activates CGRP release
contributing to acute lung injury (pulmonary edema with acute phase
cytokine/mediator release, with immunologic milieu shift toward
TH17 cytokines) followed by chronic lung injury with hyaline
membrane formation, fibrosis and reduced diffusion capacity.
Acute respiratory distress syndrome (ARDS), which is a common
pathway resulting from diverse types of lung injury, is part of the
pathogenic process that can occur after viral infections (see
Figure). Because COVID-19 (SARS2) infection leads to an acute
insult of pulmonary epithelia, it is hypothesized that a CGRP
receptor antagonist may potentially blunt the severe inflammatory
response at the alveolar level, delaying or reversing the path
towards oxygen desaturation, ARDS, requirement for supplemental
oxygenation, artificial ventilation or death.
Biohaven is also involved in COVID-19 antiviral therapy
development through its investment and clinical operations support
that it provides to Kleo Pharmaceuticals, Inc. Kleo Pharmaceuticals
is an immune-focused, biotech company with a platform of small
molecules that is working to create "synthetic vaccines" to
redirect the patient's own immune cells to attack viruses. Kleo
Pharmaceuticals recently announced that it has entered into a
research collaboration with South
Korea-based Green Cross LabCell (GCLC), a pioneer in the
next generation of allogeneic, or "off-the-shelf" natural killer
(NK) cell therapies, to rapidly advance testing of both advanced
technology platforms in combination as a potential therapy for
COVID-19 patients.
About COVID-19
COVID-19 is a novel, highly contagious
coronavirus that was first identified in December 2019. As of April
8, 2020,, there are over 1.5 million confirmed
cases worldwide, and over 420,000 cases in the US alone. Over
14,000 people in the US have died to date. The disease causes a
respiratory illness (like the flu) with symptoms such as a cough,
fever, loss of smell, and in more severe cases, difficulty
breathing. The mainstay of clinical management is largely
symptomatic treatment, with organ support in intensive care for
seriously ill patients. There is evidence that progression to the
most serious type of COVID-19 infection is related to a
hyper-immune response.
About Vazegepant
Vazegepant is a third generation,
high affinity, selective and structurally unique, small molecule
CGRP receptor antagonist from Biohaven's NOJECTION™ Migraine
Platform and the only intranasal CGRP receptor antagonist in late
stage development. The efficacy and safety profile of vazegepant
for the acute treatment of migraine, as compared to placebo, was
shown in a randomized controlled Phase 2/3 dose-ranging trial with
a total of over 1000 patients who received vazegepant. More
information about vazegepant can be found at the Biohaven's
website:
https://www.biohavenpharma.com/science-pipeline/cgrp/bhv-3500
About Kleo Pharmaceuticals, Inc.
Kleo
Pharmaceuticals is a unique immuno-oncology company developing
next-generation bispecific compounds designed to emulate or enhance
the activity of biologics based on the groundbreaking research of
its scientific founder Dr. David
Spiegel at Yale University. Similar to complex
biologic drugs, Kleo's compounds recruit the immune system to
destroy cancer cells, with the advantage of being smaller and more
versatile, leading to potentially improved safety and efficacy over
biologics. They are also much faster and more efficient to design
and produce, particularly against novel targets. Kleo is advancing
several drug candidates based on its proprietary technology
platforms, all of which are modular in design and enable rapid
generation of novel immunotherapies that can be optimized against
certain cancers, or enhance the properties of existing
immunotherapies. These include ARMs™ Antibody Recruiting Molecules
, MATEs™ Monoclonal Antibody Therapy Enhancers , and SyAMs™
Synthetic Antibody Mimics. Biohaven Pharmaceutical Holding Company
(NYSE:BHVN) and PeptiDream Inc. (Nikkei: PPTDF) are investors in
Kleo Pharmaceuticals. For more information visit
http://kleopharmaceuticals.com.
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 NURTEC™
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 http://biohavenpharma.com.
Forward-looking Statement
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 "may", "advancing" and "will" and similar expressions,
are intended to identify forward-looking statements. These
forward-looking statements involve substantial risks and
uncertainties, including statements that are based on the current
expectations and assumptions of the Biohaven's management about
vazegepant as an acute treatment for patients with migraine or
COVID-19. Forward-looking statements include those related to: the
Biohaven's ability to advance vazegepant to a Phase 3 clinical
trial, complying with applicable U.S. regulatory requirements,
the expected timing, commencement and outcomes of the 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, the potential commercialization
of vazegepant and the Biohaven's other product candidates, the
potential for the Biohaven's product candidates to be first in
class or best in class therapies and the effectiveness and safety
of the Biohaven's product candidates. 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. Additional important factors to be considered in
connection with forward-looking statements are described in the
"Risk Factors" section of the Biohaven's Annual Report on Form 10-K
filed with the Securities and Exchange Commission on February 26, 2020. The forward-looking statements
are made as of this date and the 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.
Biohaven Contact
Vlad
Coric, M.D.
Chief Executive Officer
Vlad.Coric@biohavenpharma.com
Kleo Contact
Doug
Manion, M.D.
Chief Executive Officer
dmanion@kleopharmaceuticals.com
NURTEC is a trademark of Biohaven Pharmaceutical Holding Company
Ltd.
ARMs, MATEs and SyAMs are trademarks of Kleo Pharmaceuticals,
Inc.
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