PLYMOUTH MEETING, Pa.,
March 1, 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 it met primary and secondary endpoints
among all evaluable subjects for the REVEAL 1 trial. This trial is
one of two ongoing pivotal, randomized, double-blind, multi-center,
placebo-controlled, Phase 3 trials (REVEAL 1 and REVEAL 2)
evaluating the safety, tolerability and efficacy of VGX-3100 to
treat HPV-16/18-associated cervical high-grade squamous
intraepithelial lesions (HSIL) using the company's proprietary
CELLECTRA® 5PSP device.
The trial protocol-defined modified intention to treat (mITT)
population (N=193) includes all subjects with endpoint data. For
the primary endpoint of histopathological regression of HSIL
combined with virologic clearance of HPV-16 and/or HPV-18 at week
36, the percentage of responders was 23.7% (31/131) in the
treatment group, versus 11.3% (7/62) in the placebo group (p=0.022;
12.4% difference in percentage, 95%CI: 0.4,22.5), thus achieving
statistical significance. All secondary efficacy endpoints were
achieved. These endpoints were: a) regression of cervical HSIL to
normal tissue combined with HPV-16/18 viral clearance, b)
regression of cervical HSIL alone, c) regression of cervical HSIL
to normal tissue, and d) HPV-16/18 viral clearance alone.
The trial protocol-defined intention to treat (ITT) population
(N=201) includes all randomized subjects regardless of availability
of endpoint data and defines those without endpoint data as
non-responders. There were eight such subjects (seven in the
treatment group, one in the placebo group). Including subjects with
missing endpoint data, the percentage of subjects meeting the
primary endpoint was 22.5% (31/138) in the treatment group, versus
11.1% (7/63) in the placebo group (p=0.029; 11.4% difference in
percentage, 95%CI: -0.4,21.2), which was not statistically
significant. All secondary endpoints were achieved except for
regression of cervical HSIL alone (12.8% difference in percentage,
95%CI: -0.6,24.5). The reasons for missing endpoint data were: one
subject was randomized but was never dosed, one withdrawal due to
pregnancy, one withdrawal due to administration error, one
withdrawal due to post-administration pain, one loss of follow-up
due to COVID19-related travel restrictions, and three losses to
follow up due to undetermined reasons. A pre-specified per-protocol
(PP) analysis will also be performed upon trial completion.
There were no treatment-related serious adverse events and most
adverse events were self-resolving and were considered to be mild
to moderate, consistent with earlier clinical trials.
REVEAL 1 and REVEAL 2 are designed to assess and confirm the
safety, tolerability, and efficacy of VGX-3100. INOVIO will
continue to follow subjects in REVEAL 1 for safety and durability
of response for 18 months following the last administration and
REVEAL 2 is currently enrolling subjects. INOVIO expects to present
REVEAL 1 findings at a scientific meeting this year.
Dr. J. Joseph Kim, President and
CEO of INOVIO, said, "INOVIO is very proud to advance VGX-3100 as
the first DNA medicine to achieve efficacy endpoints in a Phase 3
clinical trial in all evaluable subjects. We expect VGX-3100, if
approved, to be an important therapeutic option for those impacted
by HPV-16-/18-related disease. The REVEAL 1 efficacy and safety
data also represent an important proof-of-platform for INOVIO's DNA
medicines.
Dr. Mark Einstein, MD, MS, FACS,
FACOG, Principal Coordinating Investigator for the REVEAL 1 trial,
said, "There is a very significant need for a non-surgical
therapeutic for young women suffering from HPV-associated cervical
dysplasia. These results are very encouraging and show that
we are headed in the right direction."
Dr. Prakash Bhuyan, MD, PhD,
Senior Vice President and Head of HPV Therapeutic Clinical
Development at INOVIO, said, "We thank the investigators, site
personnel, and patients who made this research possible. We are
excited to be developing a new therapeutic designed to advance
women's health. Through our ongoing partnership with QIAGEN, we
also plan to develop complementary a biomarker diagnostic test that
would enable practitioners to more effectively identify women
expected to respond to VGX-3100."
Biomarker Development
In the course of the REVEAL 1 and REVEAL 2 clinical trials,
INOVIO continues to pursue development of a pre-treatment RNA-based
biomarker blood test which could be used to identify prospective
VGX-3100 patients who would be most likely to respond to the
immunotherapy. INOVIO believes this will be an important element of
VGX-3100 product and market development.
INOVIO announced in February that it is continuing its
partnership with QIAGEN to co-develop an in-vitro diagnostic based
on RNA sequencing technology to guide clinical decision-making for
the use of VGX-3100 in cervical HSIL. This technology had
previously been employed in a post-hoc assessment of VGX-3100 Phase
2 data by INOVIO, in which 85% of VGX-3100 treated subjects who had
the biomarker experienced regression of HPV-16- and/or
HPV-18-associated cervical HSIL.
VGX-3100 REVEAL 1 Phase 3 Cervical Dysplasia Trial Design
& Highlights
- Trial participants included 201 women, 18 years of age or
older, who have histologically-confirmed cervical HSIL associated
with HPV-16 and/or HPV-18, but who were otherwise healthy.
(ClinicalTrials.gov Identifier: NCT03185013)
- Participants received either VGX-3100 or placebo at 0, 4 and 12
weeks (randomized 2:1).
- Trial had 90% statistical power (two-sided 0.05 alpha-level)
for the evaluation of the primary endpoint
- Results are based on the demonstration of having no evidence of
HSIL associated with HPV-16 and/or HPV-18 from cervical biopsy
samples and non-detectability of HPV-16 and/or HPV-18 using the
cobas® HPV test from ThinPrep samples, at approximately 6 months
following VGX-3100 or placebo administration.
- Based upon blinded aggregate data, the overall safety findings
have been consistent with previously reported trials and considered
generally safe and well tolerated.
- Data will continue to be collected until the end of the trial
(week 88).
About High Grade Cervical Dysplasia (Cervical HSIL)
Cervical HSIL is the pre-cancerous condition of the cervix that
immediately precedes the development of invasive cervical cancer.
Cervical HSIL is caused by persistent infection with high risk-HPV,
including HPV-16 and HPV-18, which collectively confer the highest
risk for cervical HSIL development and cervical cancer development.
Estimates of the incidence rate of cervical HSIL over recent years
have indicated that up to 195,000 cases are diagnosed in the U.S.
annually.
About VGX-3100
VGX-3100 is a DNA medicine in clinical trials for the treatment
of three HPV-16-/18-related disease states – cervical dysplasia,
vulvar dysplasia and anal dysplasia. The cervical dysplasia program
is in late Phase 3 clinical trials (REVEAL 1 and REVEAL 2).
VGX-3100 is designed to utilize the patient's own immune system to
clear HPV-16/18 virus and HPV-16-/18-associated high-grade
precancerous lesions with the aim of reducing the risk of
cancer.
About INOVIO's DNA Medicines Platform
INOVIO has 15 DNA medicine clinical programs currently in
development focused on HPV-associated diseases, cancer, and
infectious diseases, including coronaviruses associated with
COVID-19 and MERS for which programs are being developed with
funding support from the U.S. Department of Defense and the
Coalition for Epidemic Preparedness Innovations (CEPI). DNA
medicines are composed of optimized 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 DNA medicines 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, such as mRNA. 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 is designed to
ensure that the DNA medicine is efficiently delivered directly into
the body's cells, where it can go to work to drive an immune
response. INOVIO's DNA medicines do not interfere with or change in
any way an individual's own DNA. The advantages of INOVIO's DNA
medicine platform are how fast DNA medicines can be designed and
manufactured; the stability of the products, which do not require
freezing in storage and transport; and the robust immune response,
safety profile, and tolerability that have been observed in
clinical trials.
With more than 3,000 patients receiving INOVIO investigational
DNA medicines in more than 7,000 applications across a range of
clinical trials, INOVIO has a strong track record of rapidly
generating DNA medicine candidates with potential to meet urgent
global health needs.
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 and only company to have clinically
demonstrated that a DNA medicine can be delivered directly into
cells in the body via a proprietary smart device to produce a
robust and tolerable immune response. INOVIO's lead immunotherapy
candidate, VGX-3100, currently in Phase 3 trials for precancerous
cervical dysplasia, cleared high-risk HPV-16 and/or HPV-18 in a
Phase 2b clinical trial. High-risk
HPV is responsible for 70% of cervical cancer, 91% of anal cancer,
and 69% of vulvar cancer. Also in development are programs
targeting HPV-related cancers and a rare HPV-related disease,
recurrent respiratory papillomatosis (RRP); non-HPV-related cancers
glioblastoma multiforme (GBM) and prostate cancer; as well as
infectious disease DNA vaccine development programs in
coronaviruses associated with COVID-19 diseases and MERS, Lassa
fever, Ebola, and HIV. Partners and collaborators include
Advaccine, ApolloBio Corporation, AstraZeneca, The Bill &
Melinda Gates Foundation, Coalition for Epidemic Preparedness
Innovations (CEPI), Defense Advanced Research Projects Agency
(DARPA)/Joint Program Executive Office for Chemical, Biological,
Radiological and Nuclear Defense (JPEO-CBRND)/Department of Defense
(DoD), HIV Vaccines Trial Network, International Vaccine Institute
(IVI), Kaneka Eurogentec, Medical CBRN Defense Consortium (MCDC),
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.
INOVIO also is a proud recipient of 2020 Women on Boards "W"
designation recognizing companies with more than 20% women on their
board of directors. For more information,
visit www.inovio.com.
CONTACTS:
Investors: Ben Matone,
484-362-0076, ben.matone@inovio.com
Media: Jeff Richardson,
267-440-4211, jrichardson@inovio.com
This press release contains certain forward-looking
statements relating to our business, including our plans to develop
VGX-3100 for HPV-16/18-associated cervical high-grade squamous
intraepithelial lesions, plans to present clinical data at an
upcoming scientific meeting, the advantages and potential benefits
of our DNA medicines platform, as well as VGX-3100 and our other
product candidates, and our expectations regarding our research and
development programs, including our plans for a collaboration with
QIAGEN to develop an in-vitro diagnostic to guide clinical decision
making for the use of VGX-3100. Actual events or results may differ
from the expectations set forth herein as a result of a number of
factors, including uncertainties inherent in preclinical 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 product
candidates, 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 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.
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SOURCE INOVIO Pharmaceuticals, Inc.