PLYMOUTH MEETING, Pa.,
Jan. 6, 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 positive efficacy results for an
open-label Phase 2 trial of VGX-3100 to treat HPV-16 and
HPV-18-associated vulvar dysplasia. A 25% or more reduction in
HPV-16/18-associated vulvar HSIL (high-grade squamous
intraepithelial lesion) was observed for 63% of trial participants
(12 of 19) treated with VGX-3100 at six months post-treatment.
Three out of the 20 participants with histology data (15%) resolved
their vulvar HSIL and had no HPV-16/18 virus detectable in the
healed area. By comparison, the spontaneous resolution of vulvar
HSIL caused by HPV-16/18 is estimated to be only 2%. The trial also
showed VGX-3100 to be safe and well-tolerated. Based upon these
results INOVIO is planning to pursue Phase 3 development.
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 Phase 2 clinical trial said, "These Phase 2
efficacy results are a very promising non-surgical advance for a
recalcitrant disease that normally requires repetitive ablation and
excision procedures to achieve disease and risk reduction, and may
offer a more safe, tolerable and efficacious treatment option for
patients."
Prakash Bhuyan, M.D., Ph.D.,
Senior Vice President and Head of HPV Therapeutic Clinical
Development at INOVIO, said, "The reduction of precancerous disease
offers a meaningful improvement in the management of this
devastating disease and is a step forward towards the enhancement
of women's healthcare."
VGX-3100 Phase 2 Vulvar Dysplasia Trial Highlights
- Trial participants were 24 women between 22 and 70 years of age
at entry and other than having HSIL were healthy.
- 80% (20/25) had VIN3 disease (the more severe form of VIN) and
88% (22/25) had a history of 1 or more recurrences
- There were no discontinuations due to adverse events; five
participants elected to withdraw for reasons unrelated to adverse
events.
- 19 participants had digital photography data, and 12 (63%) had
clinically significant lesion reduction as defined by a reduction
of lesion area of more than 25%.
- 20 participants had histology and virology data and 3 (15%)
resolved their vulvar HSIL and had no HPV-16/18 virus detectable in
the healed area.
- Histology was assessed by up to two independent pathologists
and non-detectability of HPV-16/18 from lesion tissue using PCR
(polymerase chain reaction)-based testing, at six months following
the administration of VGX-3100.
- Efficacy endpoints were measured six months
post-treatment.
- Safety will continue to be assessed for 18 months following the
last dose.
- The most observed adverse event was injection site pain, the
majority of which were mild-to-moderate.
- No cases of vulvar cancer have been observed in the trial.
For more information about the Phase 2 clinical trial, please
visit www.clinicaltrials.gov (search identifier NCT03180684).
About Vulvar Dysplasia
Vulvar dysplasia is a rare disease that affects women in
immunocompetent and immunocompromised populations. Fewer than 2% of
women with HPV-16/18-associated precancerous vulvar dysplasia
exhibit spontaneous resolution. HPV-16/18-associated precancerous
vulvar lesions (vulvar HSIL) are known to be difficult to treat,
and typically require repeat ablation and excision procedures to
achieve disease and risk reduction. Without adequate treatment
vulvar HSIL can progress to vulvar cancer. In 2017, vulvar cancer
was diagnosed in 1354 women in the U.S. and 411 died from vaginal
cancer.1
About VGX-3100
VGX-3100 is a DNA medicine in clinical trials for the treatment
of three HPV-16/18 related disease states – anal dysplasia, vulvar
dysplasia and cervical dysplasia. The cervical dysplasia program is
in late Phase 3 clinical trials (REVEAL1 and REVEAL2). VGX-3100 is
designed to utilize the patient's own immune system to clear
HPV-16/18-associated high-grade precancerous lesions with the aim
of reducing the risk of cancer.
About INOVIO's HPV-Associated DNA Medicines Clinical
Programs
This Phase 2 clinical trial builds on significant clinical
benefits demonstrated with INOVIO's HPV-associated DNA medicines
across multiple clinical trials. Specifically, VGX-3100 in a Phase
2 proof-of-concept trial for cervical dysplasia demonstrated a
response in 43 out of 107 patients in regression of high-grade
cervical lesions and elimination of the underlying HPV
infection2. A Phase 2 trial of VGX-3100 in the treatment
of anal HSIL was also conducted with positive efficacy
results3. 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 trial experienced a
long-term complete response for more two years and counting; 18 out
of 22 head and neck patients treated with MEDI0457 have not
progressed for over four years post-treatment. 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 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 MERS
and COVID-19 diseases being developed under grants from the
Coalition for Epidemic Preparedness Innovations (CEPI) and the U.S.
Department of Defense. 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 ensures 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 2,000 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. Specifically, INOVIO's lead
candidate VGX-3100, currently in Phase 3 trials for precancerous
cervical dysplasia, 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, 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 externally funded infectious disease DNA vaccine
development programs in Zika, Lassa fever, Ebola, HIV, and
coronaviruses associated with 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 (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
and manufacture DNA medicines, our expectations regarding our
research and development programs, 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 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 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, our Quarterly Report on Form
10-Q for the quarter ended September 30,
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.
1 https://www.cdc.gov/cancer/vagvulv/statistics/#Ref2
accessed on 04JAN2021
2 Trimble et al., Lancet, 386, 10008, P2078-2088,
2015; https://doi.org/10.1016/S0140-6736(15)00239-1
3 Presented at ASCCP 2020 Scientific Meeting
View original
content:http://www.prnewswire.com/news-releases/inovios-vgx-3100-demonstrates-positive-phase-2-efficacy-in-treatment-of-precancerous-vulvar-dysplasia-caused-by-hpv-1618-301201664.html
SOURCE INOVIO Pharmaceuticals, Inc.