PRINCETON, N.J., July 27, 2017 /PRNewswire/ -- Soligenix,
Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage
biopharmaceutical company focused on developing and commercializing
products to treat rare diseases where there is an unmet medical
need, announced today that patient enrollment has been opened for
its Phase 3, multinational, randomized, double-blind,
placebo-controlled study evaluating SGX942 (dusquetide) as a
treatment for severe oral mucositis in patients with head and neck
cancer receiving chemoradiation therapy (CRT).
Soligenix has been working with leading oncology centers, a
number of which participated in the Phase 2 study, to advance this
Phase 3 clinical trial referred to as the "DOM–INNATE" study
(Dusquetide treatment in Oral Mucositis – by modulating INNATE
immunity).
Based on the positive and previously published Phase 2 results
(Study IDR-OM-01), the pivotal Phase 3 clinical trial (Study
IDR-OM-02) will be a highly powered, double-blind, randomized,
placebo-controlled, multinational trial that will seek to enroll
approximately 190 subjects with squamous cell carcinoma of the oral
cavity and oropharynx who are scheduled to receive a minimum total
cumulative radiation dose of 55 Gy fractionated as 2.0-2.2 Gy per
day with concomitant cisplatin chemotherapy given as a dose of
80-100 mg/m2 every third week. Subjects will be
randomized to receive either 1.5 mg/kg SGX942 or placebo given
twice a week during and for two weeks following completion of CRT.
The primary endpoint for the study will be the median duration of
severe oral mucositis, which will be assessed by oral examination
at each treatment visit and then through six weeks following
completion of CRT. Oral mucositis will be evaluated using the WHO
Grading system. Severe oral mucositis is defined as a WHO Grade of
≥3. Subjects will be followed for an additional 12 months after the
completion of treatment.
The study design incorporates feedback from the US Food and Drug
Administration (FDA) as well as from the European Medicines Agency
(EMA) via the Scientific Advice process. The Scientific
Advice from the EMA indicates that a single, double-blind,
placebo-controlled, multinational, Phase 3 pivotal study, if
successful, in conjunction with results from the Phase 2
dose-ranging study, generally will be considered sufficient to
support a marketing authorization application for potential
licensure in Europe.
"Oral mucositis remains a debilitating side effect of cancer
treatments and is particularly severe and prevalent in head and
neck cancer patients, where there is currently no approved drug
therapy," stated Stephen T. Sonis,
DMD, DMSc, Clinical Professor of Oral Medicine at Harvard School of Dental Medicine and Chair of the
Soligenix Oral Mucositis Medical Advisory Board. "Our current
understanding of oral mucositis highlights the role of the innate
immune response in exacerbating the damage done by CRT. As
SGX942 is the first innate defense regulator in development for
oral mucositis and has previously demonstrated positive results in
a Phase 2 clinical trial, it may have the potential to offer a
promising option to treat the extremely devastating consequences of
CRT."
"We are pleased to initiate the pivotal Phase 3 study that
incorporates feedback from both the FDA and EMA, and that has the
potential to support marketing approval in both the US and the
European Union," stated Richard C.
Straube, MD, Senior Vice President and Chief Medical Officer
of Soligenix. "In an effort to better maintain study quality
and more effectively manage clinical expense, we intend to begin
with a controlled roll-out of US study sites, followed by the
addition of European centers in early 2018. This will allow
us to first ensure protocol adherence in the US before expansion of
the study to centers outside the US. We look forward to
advancing this pivotal trial in an effort to address the
significant unmet medical need that currently exists in this
patient population."
The Phase 2 oral mucositis clinical study was partially funded
with a grant from the National Institute of Dental and Craniofacial
Research Small Business Innovation Research grant #1R43 DE024032-01
(Soligenix, Inc.).
About SGX942
Dusquetide (the active ingredient in SGX942) is an innate
defense regulator (IDR), a new class of short, synthetic
peptides. It has a novel mechanism of action whereby it
modulates the body's reaction to both injury and infection towards
an anti-inflammatory and an anti-infective response. IDRs
have no direct antibiotic activity but, by modulating the host's
innate immune system responses, increase survival after infections
caused by a broad range of bacterial Gram-negative and
Gram-positive pathogens. It also accelerates resolution of
tissue damage following exposure to a variety of agents including
bacterial pathogens, trauma and chemo- and/or radiation
therapy. Preclinical efficacy and safety has been
demonstrated in numerous animal disease models including mucositis,
colitis, melioidosis, macrophage activation syndrome (MAS) and
other bacterial infections. Some of these preclinical
findings have been published in an article entitled "A novel
approach for emerging and antibiotic resistant infections: Innate
defense regulators as an agnostic therapy," available at the
following link:
http://dx.doi.org/10.1016/j.jbiotec.2016.03.032.
SGX942 has demonstrated safety in a Phase 1 clinical study in 84
healthy human volunteers. Recently, SGX942 had positive
results in an exploratory Phase 2 clinical study in 111 patients
with oral mucositis due to CRT for head and neck cancer
(HNC). Consistent with preclinical findings, SGX942 at a dose
of 1.5 mg/kg demonstrated positive improvements in decreasing the
duration of severe oral mucositis by 50% overall compared to the
placebo group, from 18 days to 9 days (p=0.099). In patients
at the highest risk of developing severe oral mucositis (i.e.,
those receiving concomitant cisplatin chemotherapy of 80-100
mg/m2 every third week), the reduction in the duration
of severe oral mucositis was even more significant at 67% when
treated with SGX942 1.5 mg/kg, from 30 days to 10 days
(p=0.04). The p-values met the prospectively defined
statistical threshold of p<0.1 in the study protocol.
Additional observations included an improved tumor response to CRT
at the one month follow-up visit, as well as decreases in mortality
and infection rate. The study results are reviewed in
"Dusquetide: A Novel Innate Defense Regulator Demonstrating a
Significant and Consistent Reduction in the Duration of Oral
Mucositis in Preclinical Data and a Randomized, Placebo-Controlled
Phase 2 Clinical Study," published online in the Journal of
Biotechnology and available at the following link:
http://dx.doi.org/10.1016/j.jbiotec.2016.10.010.
Long-term (12 month) follow-up data further indicated the safety
and tolerability of SGX942 treatment, with a sustained trend
towards reduced mortality and increased tumor resolution in the 1.5
mg/kg SGX942 treatment group compared to the placebo group.
Opioid pain medication use was also seen to decrease over the
course of CRT in the 1.5 mg/kg SGX942 treatment group at the point
of highest oral mucositis risk, while it increased in the placebo
group. Detailed clinical results from the Phase 2 study, as
well as a review of the pathogenesis of oral mucositis and the
mechanism of action of SGX942, are discussed here. The long-term
follow-up results from the Phase 2 study are reviewed in,
"Dusquetide: Reduction in Oral Mucositis associated with Enduring
Ancillary Benefits in Tumor Resolution and Decreased Mortality in
Head and Neck Cancer Patients", published online in
Biotechnology Reports and available at the following link:
https://doi.org/10.1016/j.btre.2017.05.002.
The Phase 2 oral mucositis clinical study was partially funded
with a grant from the National Institute of Dental and Craniofacial
Research Small Business Innovation Research grant #1R43 DE024032-01
(Soligenix, Inc.).
Drug products containing dusquetide have also received Fast
Track Designations from the FDA for the treatment of oral mucositis
as a result of radiation and/or chemotherapy treatment in HNC
patients, and as an adjunctive therapy with other antibacterial
drugs, for the treatment of melioidosis. Orphan Drug Designations
for use of dusquetide in the treatment of MAS as well as for the
treatment of acute radiation syndrome have also been granted. In
addition, dusquetide has been granted Promising Innovative Medicine
designation in the United Kingdom
by the Medicines and Healthcare Products Regulatory Agency for the
treatment of severe oral mucositis in HNC patients receiving
CRT.
Dusquetide and related analogs have a strong intellectual
property position, including composition of matter.
Dusquetide was developed pursuant to discoveries made by Professors
B. Brett Finlay, PhD and
Robert Hancock, PhD of the
University of British Columbia,
Canada.
About Oral Mucositis
Mucositis is the clinical term for damage done to the mucosa by
anticancer therapies. It can occur in any mucosal region, but
is most commonly associated with the mouth, followed by the small
intestine. It is estimated, based upon review of historic
published studies and reports and an interpolation of data on the
incidence of mucositis, that mucositis affects approximately
500,000 people in the US per year and occurs in 40% of patients
receiving chemotherapy. Mucositis can be severely
debilitating and can lead to infection, sepsis, the need for
parenteral nutrition and narcotic analgesia. The
gastrointestinal damage causes severe diarrhea. These
symptoms can limit the doses and duration of cancer treatment,
leading to sub-optimal treatment outcomes.
The mechanisms of mucositis have been extensively studied and
have been recently linked to the interaction of chemotherapy and/or
radiation therapy with the innate defense system. Bacterial
infection of the ulcerative lesions is now regarded as a secondary
consequence of dysregulated local inflammation triggered by
therapy-induced cell death, rather than as the primary cause of the
lesions.
It is estimated, based upon review of historic published studies
and reports and an interpolation of data on the incidence of oral
mucositis, that oral mucositis in HNC is a subpopulation of
approximately 90,000 patients in the US, with a comparable number
in Europe. Oral mucositis almost always occurs in patients
with HNC treated with chemoradiation therapy and is severe, causing
inability to eat and/or drink, in >80% of patients. It is common
(40-100% incidence) in patients undergoing high dose chemotherapy
and hematopoietic cell transplantation, where the incidence and
severity of oral mucositis depends greatly on the nature of the
conditioning regimen used for myeloablation.
Oral mucositis in HNC remains an area of unmet medical need
where there are currently no approved drug therapies.
About Soligenix, Inc.
Soligenix is a late-stage biopharmaceutical company focused on
developing and commercializing products to treat rare diseases
where there is an unmet medical need. Our BioTherapeutics business
segment is developing SGX301 as a novel photodynamic therapy
utilizing safe visible light for the treatment of cutaneous T-cell
lymphoma, our first-in-class innate defense regulator (IDR)
technology, dusquetide (SGX942) for the treatment of oral mucositis
in head and neck cancer, and proprietary formulations of oral
beclomethasone 17,21-dipropionate (BDP) for the
prevention/treatment of gastrointestinal (GI) disorders
characterized by severe inflammation including pediatric Crohn's
disease (SGX203) and acute radiation enteritis (SGX201).
Our Vaccines/BioDefense business segment includes active
development programs for RiVax®, our ricin toxin vaccine
candidate, OrbeShield®, our GI acute radiation syndrome
therapeutic candidate and SGX943, our therapeutic candidate for
antibiotic resistant and emerging infectious disease. The
development of our vaccine programs incorporates the use of our
proprietary heat stabilization platform technology, known as
ThermoVax®. To date, this business segment has
been supported with government grant and contract funding from the
National Institute of Allergy and Infectious Diseases (NIAID) and
the Biomedical Advanced Research and Development Authority
(BARDA).
For further information regarding Soligenix, Inc., please visit
the Company's website at www.soligenix.com.
This press release may contain forward-looking statements that
reflect Soligenix, Inc.'s current expectations about its future
results, performance, prospects and opportunities, including but
not limited to, potential market sizes, patient populations and
clinical trial enrollment. These statements are made pursuant to
the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995. Statements that are not historical facts, such
as "anticipates," "estimates," "believes," "hopes," "intends,"
"plans," "expects," "goal," "may," "suggest," "will," "potential,"
or similar expressions, are forward-looking statements. These
statements are subject to a number of risks, uncertainties and
other factors that could cause actual events or results in future
periods to differ materially from what is expressed in, or implied
by, these statements. Soligenix cannot assure you that it
will be able to successfully develop, achieve regulatory approval
for or commercialize products based on its technologies,
particularly in light of the significant uncertainty inherent in
developing therapeutics and vaccines against bioterror threats,
conducting preclinical and clinical trials of therapeutics and
vaccines, obtaining regulatory approvals and manufacturing
therapeutics and vaccines, that product development and
commercialization efforts will not be reduced or discontinued due
to difficulties or delays in clinical trials or due to lack of
progress or positive results from research and development efforts,
that it will be able to successfully obtain any further funding to
support product development and commercialization efforts,
including grants and awards, maintain its existing grants which are
subject to performance requirements, enter into any biodefense
procurement contracts with the US Government or other countries,
that it will be able to compete with larger and better financed
competitors in the biotechnology industry, that changes in health
care practice, third party reimbursement limitations and Federal
and/or state health care reform initiatives will not negatively
affect its business, or that the US Congress may not pass any
legislation that would provide additional funding for the Project
BioShield program. In addition, there can be no assurance as to the
timing or success of the Phase 3 clinical trial of SGX942
(dusquetide) as a treatment for oral mucositis in patients with
head and neck cancer receiving chemoradiation therapy and the Phase
3 clinical trial of SGX301 (synthetic hypericin) for the treatment
of cutaneous T-cell lymphoma. These and other risk factors are
described from time to time in filings with the Securities and
Exchange Commission, including, but not limited to, Soligenix's
reports on Forms 10-Q and 10-K. Unless required by law,
Soligenix assumes no obligation to update or revise any
forward-looking statements as a result of new information or future
events.
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SOURCE Soligenix, Inc.