PLYMOUTH MEETING, Pa.,
Nov. 16, 2021 /PRNewswire/
-- INOVIO (NASDAQ: INO), a biotechnology company focused on
bringing to market precisely designed DNA medicines to treat and
protect people from infectious diseases, cancer, and HPV-associated
diseases, today announced that several volunteers have been dosed
with its DNA-based, intradermal Ebola vaccine candidate, INO-4201,
as part of a randomized, placebo-controlled, Phase 1b clinical trial (NCT04906629). The trial will
assess whether INO-4201 can be used as a booster in healthy
volunteers previously vaccinated with rVSV-ZEBOV
(Ervebo®1), an FDA- and EMA-approved viral-based vector
Ebola vaccine. It follows INOVIO's pre-clinical and Phase 1 trials
which suggested to investigators that INO-4201 was well-tolerated
and resulted in 100% seroconversion after two doses.
"We are excited to begin this Phase 1b trial with our intradermal DNA vaccine
candidate INO-4201 as a potential Ebola booster vaccine," said
Laurent Humeau, Ph.D., Chief
Scientific Officer, INOVIO. "Due to the potential for anti-vector
immunity after primary Ervebo vaccination, boosting with the same
vaccine several years later may not be possible. INOVIO's DNA
vaccine candidate INO-4201 has the potential to serve as a booster
in the setting of prior Ervebo vaccination depending on its
tolerability after multiple administrations. Furthermore, our DNA
vaccine candidates could offer scalability and allow for
room-temperature storage critical to transportation within tropical
environments."
Investigators plan to recruit approximately 50 healthy
volunteers to participate in the clinical trial. The trial will
evaluate the safety, tolerability, and immunogenicity of INO-4201
in healthy adult volunteers who previously received a single
intramuscular injection of rVSV-ZEBOV (Ervebo). Ervebo is approved
by the U.S. Food and Drug Administration (FDA) for the prevention
of disease caused by Zaire
ebolavirus in individuals 18 years of age and older as a single
dose administration. Ervebo is a replication-competent, live,
attenuated recombinant vesicular stomatitis virus (rVSV) -based
vaccine.
Trial participants will be randomized to either INO-4201 or
placebo (4:1 ratio) and will receive an intradermal injection
followed by electroporation using INOVIO's CELLECTRA®
2000 smart delivery device. The primary outcome measures include
the incidence of adverse events related to INO-4201 from day 0 to
14, and levels of antibodies that bind to Ebola virus surface
glycoprotein antigen four weeks after injection.
The trial is being coordinated by GuardRX, a non-profit
organization whose goal is to spur development of and access to
life-saving therapeutics. Its sponsor is the Geneva University
Hospitals, which conducted one of the first randomized trials
testing the Ervebo vaccine in 2014. The trial is funded by the U.S.
Defense Advanced Research Projects Agency (DARPA). The information
herein does not necessarily reflect the position or the policy of
the U.S. Government, and no official endorsement should be
inferred.
Angela Huttner, M.D., Infectious
Disease Consultant, Geneva University Hospitals, and the lead
investigator of the study, said, "We are grateful to our volunteers
for their critical role in the development of this vaccine, which
we hope will be a key player in future Ebola Virus Disease
prevention."
Dr. Gary Kobinger,
microbiologist, GUARDRx ex-officio (President) and Board
Member and Director of the Galveston National Laboratory at the
University of Texas Medical Branch,
said, "Stimulating long-term protection through affordable booster
doses that have the most advantageous safety profiles has become a
priority and this is what is being addressed in this study."
INO-4201 is composed of a precisely designed DNA plasmid that is
injected intradermally followed by electroporation using a
proprietary smart device, which delivers the DNA plasmid directly
into cells in the body and is intended to produce a well-tolerated
immune response. As one of the only nucleic acid-based vaccine
candidates INO-4201 is stable at room temperature for more than a
year, at 37°C for more than a month, has a five-year projected
shelf life at normal refrigeration temperature and does not need to
be frozen during transport or storage.
About Ebola Virus Disease
The Ebola virus family includes four virus species that cause
periodic outbreaks of a highly contagious and lethal human
infectious disease – called Ebola Virus Disease (EVD) [US CDC
(2021a)]. EVD is characterized by fatigue, vomiting, diarrhea,
abdominal pain, severe hemorrhagic fever, and very often death
[Feldmann et al New Eng J Med (2020)]. The EBV case fatality ratio
(CFR) has averaged 60% to 65% across outbreaks [Nyakarahuka et al
BMC Infect Dis (2016); Kawuki et al Pub Hlth (2021)]. The virus is
transmitted from wild animals to people then easily spreads via
human-to-human transmission. Disturbingly, new research suggests
dormant Ebola virus in a previously infected survivor could
re-emerge up to nearly 5 years later and again allow human-to-human
transmission [Keita et al Nature (Sept. 15,
2021)]. Since virus discovery, the worst Ebola outbreak was
2014-2016 in West Africa,
including more than 28,000 cases, 11,000 deaths, and a few cases
that traveled to the U.S. or Europe [WHO (2021)].
Ebola virus is classified as a Category A Priority Pathogen by
the U.S. Centers for Disease Control and Prevention (CDC) [CDC
(2021b)]. This designation indicates
a national security risk, and the US FDA has an accelerated
development approval pathway for vaccines against such pathogens.
Also, the World Health Organization (WHO) continues to list Ebola
Virus Disease as a priority for research and development in
emergency contexts [WHO (2021b)] and
coordinates planning to prevent and respond to Ebola epidemics [WHO
(2016)]. (see references below)
About INOVIO's DNA Medicines Platform
INOVIO has 15 DNA vaccine candidate clinical programs currently
in development and focused on HPV-associated diseases, cancer, and
infectious diseases, including programs for Middle East Respiratory
Syndrome, Lassa Fever and COVID-19 being developed under grants
from the Coalition for Epidemic Preparedness Innovations and the
U.S. Department of Defense. Its DNA vaccine candidates are composed
of precisely designed DNA plasmids, which are small circles of
double-stranded DNA that are synthesized or reorganized by a
computer-sequencing technology and designed to produce a specific
immune response in the body.
INOVIO's vaccine candidates deliver optimized plasmids directly
into cells intramuscularly or intradermally using INOVIO's
proprietary hand-held smart device called CELLECTRA®. The
CELLECTRA®️ device uses a brief electrical pulse to reversibly open
small pores in the cell to allow the plasmids to enter, overcoming
a key limitation of other DNA and other nucleic acid approaches.
Once inside the cell, the DNA plasmids enable the cell to produce
the targeted antigen. The antigen is processed naturally in the
cell and triggers the desired T cell and antibody mediated immune
responses. Administration with the CELLECTRA® device allows
the vaccine candidate to be efficiently delivered directly into the
body's cells, where it can go to work to drive an immune response.
INOVIO's DNA vaccine candidates do not interfere with or change in
any way an individual's own DNA. The anticipated advantages of
INOVIO's platform are the relative speed at which DNA vaccines can
be designed and manufactured; the stability of the candidates,
which do not require freezing in storage and transport; and the
robust immune response and tolerability that have been observed
thus far in clinical trials.
More than 3,900 clinical trial participants have received
INOVIO's investigational DNA medicines in more than 12,000
applications across a range of clinical trials.
About INOVIO
INOVIO is a biotechnology company focused on rapidly bringing to
market precisely designed DNA medicines to treat and protect people
from infectious diseases, cancer, and diseases associated with HPV.
INOVIO is the first company to have clinically demonstrated that a
DNA vaccine candidate can be delivered directly into cells in the
body via a proprietary smart device to produce a robust and
tolerable immune response. Specifically, INOVIO's lead therapeutic
candidate VGX-3100 met primary and secondary endpoints for all
evaluable subjects in REVEAL 1, the first of two, Phase 3 trials
for precancerous cervical dysplasia, demonstrating ability to
destroy and clear both high-grade cervical lesions and the
underlying high-risk HPV-16/18. INOVIO is also evaluating INO-4800,
a DNA vaccine candidate against COVID-19, in a Phase 2/3 clinical
trial; the Phase 3 segment of which has received regulatory
approvals to proceed in Colombia,
Mexico, Brazil, Philippines, India, Thailand, and the
United States. INOVIO's partners, Advaccine
Biopharmaceuticals and International Vaccine Institute, are also
evaluating INO-4800 in ongoing clinical trials in China and South
Korea, respectively.
Partners and collaborators include Advaccine, ApolloBio
Corporation, AstraZeneca, The Bill & Melinda Gates Foundation,
Coalition for Epidemic Preparedness Innovations, Defense Advanced
Research Projects Agency/Joint Program Executive Office for
Chemical, Biological, Radiological and Nuclear Defense/Department
of Defense, HIV Vaccines Trial Network, International Vaccine
Institute, Kaneka Eurogentec, Medical CBRN Defense Consortium,
National Cancer Institute, National Institutes of Health, National
Institute of Allergy and Infectious Diseases, Ology Bioservices,
the Parker Institute for Cancer Immunotherapy, Plumbline Life
Sciences, Regeneron, Richter-Helm BioLogics, Thermo Fisher
Scientific, University of Pennsylvania,
Walter Reed Army Institute of Research, and The Wistar Institute.
For more information, visit www.inovio.com.
About GUARDRx
Established in 2018, Global Urgent and Advanced Research and
Development (GUARD) executes preclinical and clinical development
strategies on prophylactic and therapeutic products for neglected
diseases. GUARD is a non-profit, non-governmental organization
whose goal is to bring prophylactic and therapeutic products that
do not have a traditional commercialization pathway. GUARD is
committed to facilitating the availability of lifesaving products
to the global community including in the event of an infectious
disease emergency. GUARD expertise includes preclinical and
clinical development of vaccines and therapeutics, regulatory
submissions and production of cGMP material; humoral immune
responses evaluation using tailored sensitive plate-based ELISA;
establish & standardize new diagnostics
protocols; submission to appropriate regulatory agencies for
Therapeutic Products and Institutional Review Boards
(IRBs); production of study final reports, and award data
management.
GUARD's main objective is to accumulate clinical data packages
within rigorous regulatory processes to support further clinical
progression or long-term solutions to orphan diseases for the
betterment of the global population. For more information, visit
www.guardrx.org.
CONTACTS:
Media: Jeff Richardson,
267-440-4211, jrichardson@inovio.com
Investors: Ben Matone, 484-362-0076,
ben.matone@inovio.com
This press release contains certain forward-looking
statements relating to our business, including our plans to develop
DNA medicines, our expectations regarding our research and
development programs, including the planned initiation and conduct
of preclinical studies and clinical trials and the availability and
timing of data from those studies and trials, and our ability to
successfully manufacture and produce large quantities of our
product candidates if they receive regulatory approval. Actual
events or results may differ from the expectations set forth herein
as a result of a number of factors, including uncertainties
inherent in pre-clinical studies, clinical trials, product
development programs and commercialization activities and outcomes,
our ability to secure sufficient manufacturing capacity to mass
produce our product candidates, the availability of funding to
support continuing research and studies in an effort to prove
safety and efficacy of electroporation technology as a delivery
mechanism or develop viable DNA medicines, our ability to support
our pipeline of DNA medicine products, the ability of our
collaborators to attain development and commercial milestones for
products we license and product sales that will enable us to
receive future payments and royalties, the adequacy of our capital
resources, the availability or potential availability of
alternative therapies or treatments for the conditions targeted by
us or our collaborators, including alternatives that may be more
efficacious or cost effective than any therapy or treatment that we
and our collaborators hope to develop, issues involving product
liability, issues involving patents and whether they or licenses to
them will provide us with meaningful protection from others using
the covered technologies, whether such proprietary rights are
enforceable or defensible or infringe or allegedly infringe on
rights of others or can withstand claims of invalidity and whether
we can finance or devote other significant resources that may be
necessary to prosecute, protect or defend them, the level of
corporate expenditures, assessments of our technology by potential
corporate or other partners or collaborators, capital market
conditions, the impact of government healthcare proposals and other
factors set forth in our Annual Report on Form 10-K for the year
ended December 31, 2020, our
Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and other filings we make from
time to time with the Securities and Exchange Commission. There can
be no assurance that any product candidate in our pipeline will be
successfully developed, manufactured or commercialized, that final
results of clinical trials will be supportive of regulatory
approvals required to market products, or that any of the
forward-looking information provided herein will be proven
accurate. Forward-looking statements speak only as of the date of
this release, and we undertake no obligation to update or revise
these statements, except as may be required by law.
1 Copyright © 2019 Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc. All rights
reserved.
References
Feldmann H, Sprecher A, Geisbert TW. Ebola. N Engl J Med. 2020
May 7;382(19):1832-1842.
Kawuki J, Musa TH, Yu X. Impact of recurrent outbreaks of Ebola
virus disease in Africa: a
meta-analysis of case fatality rates. Public Health. 2021
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Keita KA, Koundouno FR, Faye M., et al. Resurgence of Ebola
virus in 2021 in Guinea suggests a
new paradigm for outbreaks. Nature (Sept.
15, 2021).
Nyakarahuka L, Kankya C, Krontveit R, Mayer B, Mwiine FN,
Lutwama J, Skjerve E. How severe and prevalent are Ebola and
Marburg viruses? A systematic review and meta-analysis of the case
fatality rates and seroprevalence. BMC Infect Dis. 2016 Nov
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Disease Control and Prevention. Ebola (Ebola Virus Disease).
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https://emergency.cdc.gov/agent/agentlist-category.asp [accessed
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https://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease
[accessed September 15, 2021]
World Health Organization (2021b).
Priority diseases for research and development in emergency
contexts.
https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts
[accessed Oct. 4, 2021].
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