PLYMOUTH MEETING, Pa.,
March 30, 2020 /PRNewswire/
-- INOVIO Pharmaceuticals, Inc. (NASDAQ: INO) today reported
interim results from an open-label Phase 2 trial designed to
evaluate the safety and efficacy of VGX-3100 in women with vulvar
dysplasia, also known as high grade squamous intraepithelial lesion
(HSIL), a precancerous condition caused by high-risk human
papillomavirus (HPV) types 16 and/or 18. A total of 22 subjects
have received all 4 doses and will be evaluated to the end of the
study. INOVIO is reporting interim data on the 10 subjects who have
completed their primary endpoint evaluation at six months following
treatment with VGX-3100. Based upon the available results, 80% (8
out of 10 subjects) had a reduction (2 cm2 on average)
in qualifying lesion area (average 60% reduction) of which 20% (2
of 10) completely resolved their vulvar HSIL and had no virus
detectable in the healed area, 6 months following treatment.
Trial results will be presented from April 1st through April 2nd at the annual
American Society for Colposcopy and Cervical Pathology (ASCCP)
meeting as a virtual session titled: "Preliminary Results of an
Open-Label Phase 2 Study of VGX-3100 for the Treatment of HPV-16
and/or HPV-18 (HPV-16/18) Related Vulvar HSIL." Safety results were
consistent with the known safety profile of VGX-3100. There were no
drug-related serious adverse events. No cases of carcinoma have
been observed.
Vulvar HSIL is an orphan condition that usually requires
surgery, which has significant physical and psychosocial impacts
(e.g. severe pain, disfigurement, sexual dysfunction). The success
of such surgery is marginal, as the recurrence rate of high grade
vulvar pre-cancer is approximately 30 to 50% three years
post-treatment. Overall less than 5% of women with vulvar HSIL
exhibit spontaneous resolution. Without adequate treatment vulvar
HSIL can progress to vulvar cancer which is projected to claim
approximately 1350 lives in the US in 2020 alone.
Dr. Prakash Bhuyan, MD PhD, Vice
President and Head of Clinical Development of HPV Therapeutics for
INOVIO said: "INOVIO is developing VGX-3100 as a comprehensive
treatment for HPV precancerous diseases. These proof-of-concept
data take us one step closer to a better approach to treat vulvar
precancer and improve women's health."
Dr. Robert Edwards, MD, Milton
Lawrence McCall Professor and Chair, Department of Obstetrics,
Gynecology & Reproductive Sciences, University of Pittsburgh and Principal Coordinating
Investigator for the trial said: "This novel platform allows
effective immune stimulations in the face of long standing viral
induced precancer for this highly morbid disease. Many of these
patients face years or sequential surgical resections and markedly
impaired sexually function, apprehension about cancer risk, and
some cases invasive cancer requiring highly morbid therapy."
VGX-3100 Safety and Efficacy Highlights for Vulvar
Dysplasia
- Safety results are consistent with the known safety profile of
VGX-3100. There were no drug-related serious adverse events.
- 80% (8 of 10 subjects) showed an overall decrease in the lesion
area six months after treatment and 20% (2 of 10 of subjects)
completely resolved their vulvar HSIL, which compares to a
spontaneous regression of 1.5% to 5%.
- Results further support proof of concept for DNA medicines as
also demonstrated in prior VGX-3100 Phase 2b study in high-risk HPV-associated precancerous
cervical dysplasia.
- Less than 5% of women with vulvar HSIL exhibit spontaneous
resolution.
- The success of surgery for vulvar HSIL is marginal, as the
recurrence rate of high grade vulvar pre-cancer is approximately 30
to 50% three years post-treatment.
About Vulvar Dysplasia (HSIL)
If left untreated vulvar pre-cancers can progress to invasive
cancer of the vulva. Approximately 27,000 cases of HPV-related
vulvar pre-cancers occur in the U.S. each year with a similar
number of estimated cases in Europe each year. HPV-16 and/or HPV-18 are
involved in about 80% of HPV-related vulvar pre-cancers cases in
the U.S. and Europe. Once vulvar
pre-cancers develop, spontaneous regression (i.e. natural
resolution of the lesion) is rare and occurs in 1.5% to 5% of
cases. An estimated 6,000 new cases of vulvar cancer occur in the
U.S. each year with about 50% to 80% of those being
HPV-associated.
About the Study
This open-label, randomized, multi-center Phase 2 study is
designed to evaluate the safety and efficacy of VGX-3100 in adult
women 18 and older, with precancerous vulvar dysplasia caused by
HPV-16 and/or HPV-18. The key efficacy measures being evaluated are
resolution of HSIL, non-detectability of HPV 16/18, and the
decrease in lesion area. 33 women received 4 doses of VGX-3100 at
Weeks 0, 4, 12, and 24, of whom 8 subjects also received topical
imiquimod, which was being evaluated as an adjunctive treatment.
Enrollment into the imiquimod arm was halted due to having no
meaningful improvement upon the efficacy of VGX-3100 alone.
Efficacy at 6 months following VGX-3100 treatment will be reported
for all participants with available data, 22 of whom received
VGX-3100 alone. Three participants have discontinued due to reasons
of moving (1 subject) and electing for earlier surgery (2
subjects). The trial will follow treated participants for up to 1
year after the 4th dose.
About INOVIO's HPV-Associated DNA Medicines Clinical
Programs
This study builds on significant clinical benefits demonstrated
with INOVIO's HPV-associated DNA medicines in multiple clinical
trials. Specifically, VGX-3100 in a Phase 2 proof-of-concept trial
for cervical dysplasia demonstrated a complete response in 43 out
of 107 patients in regression of high-grade cervical lesions and
elimination of the underlying HPV infection. Additionally, two out
of four metastatic HPV-associated head and neck cancer patients
treated with MEDI0457 and a PD-1 check point inhibitors in a Phase
1 study experienced a long-term complete response for more two
years and counting. Lastly, a pilot study of INOVIO's DNA medicine
INO-3107 in recurrent respiratory papillomatosis (RRP) resulted in
two out of two patients delaying surgery due to lack of tumor
recurrence.
About VGX-3100
VGX-3100 is a DNA medicine under Phase 3 investigation for the
treatment of HPV-16 and HPV-18 infection and precancerous lesions
of the cervix. INOVIO is in open-label Phase 2 clinical trials
evaluating its efficacy for treating HPV-related vulvar and anal
dysplasia (HSIL). VGX-3100 has the potential to be the first
approved treatment for HPV infection of the cervix and the first
non-surgical treatment for precancerous cervical lesions. It works
by stimulating a specific immune response to HPV-16 and HPV-18,
which targets the infection and causes destruction of precancerous
cells. In a randomized, double-blind, placebo-controlled phase
2b study in 167 adult women with
histologically documented HPV-16/18 cervical dysplasia (CIN2/3 or
HSIL), treatment with VGX-3100 resulted in a statistically
significantly greater regression of cervical dysplasia and
clearance of HPV-16/18 infection vs. placebo. The most common side
effect was injection site pain, and no serious adverse events were
reported. VGX-3100 utilizes the patient's own immune system to
clear HPV-16 and HPV-18 infection and precancerous lesions without
the increased risks associated with surgery, such as loss of
reproductive health and negative psychosocial impacts.
About INOVIO's DNA Medicines
INOVIO has 15 DNA medicine clinical programs currently in
development focused on HPV-associated diseases, cancer, and
infectious diseases, including coronaviruses associated MERS and
COVID-19 diseases under grants from 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®. CELLECTRA® uses a brief
electrical pulse to open small pores in the cell reversibly to
allow the plasmids to enter, overcoming a key limitation of other
DNA and mRNA approaches. Once inside the cell, the plasmids are
used by the cell's own machinery to generate specific coded
antigens, which then stimulate an immune response. Administration
with the CELLECTRA device ensures that the DNA medicine is
delivered directly into the body's cells, where it can go to work
immediately mounting 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 constructed 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 demonstrated in clinical trials.
With more than 2,000 patients receiving INOVIO investigational
DNA medicines in more than 6,000 applications across a range of
clinical trials, INOVIO has a strong track record of rapidly
generating DNA medicine candidates to meet urgent global health
needs.
About INOVIO Pharmaceuticals, Inc.
INOVIO is a biotechnology company focused on rapidly bringing to
market precisely designed DNA medicines to treat, cure, and protect
people from diseases associated with HPV, cancer, and infectious
diseases. 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. Specifically, INOVIO's lead
candidate VGX-3100, currently in Phase 3 trials for precancerous
cervical dysplasia, demonstrated it destroyed and cleared high-risk
HPV 16 and 18 in a Phase 2b clinical
trial. High-risk HPV is responsible for 70% of cervical cancer, 90%
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 externally funded infectious disease DNA vaccine
development programs in Zika, Lassa fever, Ebola, HIV, and
coronaviruses associated MERS and COVID-19 diseases. Partners and
collaborators include Advaccine, ApolloBio Corporation,
AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for
Epidemic Preparedness Innovations (CEPI), Defense Advanced Research
Projects Agency, GeneOne Life Science, HIV Vaccines Trial Network,
Medical CBRN Defense Consortium (MCDC), National Cancer Institute,
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Plumbline Life Sciences, Regeneron,
Roche/Genentech, 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.
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, as well as commercialization activities,
including the planned initiation and conduct of clinical trials,
the availability and timing of data from those trials and our
commercialization strategy and tactics. 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, 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, 2019 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.
CONTACTS:
Investors: Ben
Matone, 484-362-0076, ben.matone@inovio.com
Media:
Jeff Richardson, 267-440-4211,
jrichardson@inovio.com
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SOURCE INOVIO Pharmaceuticals, Inc.