PRINCETON, N.J., Oct. 22, 2020 /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 continued optional treatment with
SGX301 (synthetic hypericin) across all lesions during the
compassionate use, safety portion of the trial (Cycle 3), for a
total of 6 months in the study, continued to significantly improve
responses and remained safe and well-tolerated in its FLASH
(Fluorescent Light Activated Synthetic Hypericin) study. This
data reinforces the positive SGX301 primary endpoint treatment
response demonstrated in Cycle 1. SGX30l treatment in Cycle 3
further improved response rates, with 49% of patients electing to
receive SGX301 for a total of 18 weeks demonstrating a 50% or
greater reduction in their combined CAILS (Composite Assessment of
Index Lesion Score) lesion score compared to 40% of patients
demonstrating such a reduction after completing 12 weeks of SGX301
treatment in Cycle 2 (p=0.046). In addition, continued
analysis of results from the protocol mandated efficacy cycles
(Cycles 1 and 2) of the study has revealed that 12 weeks of
treatment (Cycle 2) with SGX301 is equally effective on both patch
(response 37%, p=0.0009) and plaque (response 42%, p<0.0001)
lesions of cutaneous T-cell lymphoma (CTCL) when compared to Cycle
1 placebo lesion responses, further demonstrating the unique
benefits of the more deeply penetrating visible light activation of
hypericin. SGX301 continued to be very well tolerated, benefiting
from the lack of hypericin circulation in the blood stream after
targeted topical application to the lesions, as well as the use of
visible light.
"Along with SGX301's rapid response time and safety profile, the
patch and plaque data from the study are extremely compelling,"
stated Brian Poligone, MD, PhD, Lead
Enrolling Investigator in the FLASH study and Director of the
Rochester Skin Lymphoma Medical Group, Fairport, NY, USA. "Current treatments
for CTCL are generally less effective against plaques and deeper
lesions, very similar to the problem observed in psoriasis.
The ability of SGX301 to target both patches and thicker plaques in
CTCL is an important feature for this therapy and, if approved,
will be of benefit to patients, regardless of their
presentation. These results are consistent with the positive
findings highlighted in a recently reported case study of
folliculotropic mycosis fungoides, a hard to treat variant of CTCL
where lesions are associated with the hair follicles deep in the
skin and more resistant to phototherapy."
"On behalf of everyone at Soligenix, I would like to extend my
sincere thanks to the patients, families, investigators, and
advisors involved in the pivotal Phase 3 FLASH study," stated
Richard Straube, MD, Chief Medical
Officer of Soligenix. "In treating CTCL, which is a chronic
cancer with no cure, long-term safety is of paramount
concern. SGX301 treatment continues to demonstrate strong
efficacy and a very benign safety profile, which is of significant
benefit to patients living with this difficult disease.
Although the focus of the additional optional cycle was safety, we
continue to see improvement in CTCL lesions with extended SGX301
treatment, building upon the robust efficacy signal in previous
cycles. The efficacy against both patch and plaque lesions,
for example, is particularly encouraging and we believe provides
another important differentiating feature from other therapies
currently being used to treat early stage disease."
"These results continue to strengthen our long-standing belief
that SGX301 has the potential to be a valuable and life-changing
therapy for patients suffering from CTCL, which is an orphan
disease and area of unmet medical need," stated Christopher J. Schaber, PhD, President and Chief
Executive Officer of Soligenix. "With the study now
concluding, we continue to thoroughly assess commercialization
and/or partnership of SGX301 while in parallel preparing for filing
the New Drug Application with FDA. Despite the challenges
imposed by the COVID-19 pandemic, 2020 continues to be a very
impactful year for us as we now focus on our next near-term and
potentially transformational catalyst - the announcement of
top-line final results by year-end from our other pivotal Phase 3
study of SGX942 (dusquetide) for the treatment of oral mucositis in
head and neck cancer patients."
Soligenix previously announced positive top-line results when
the FLASH study achieved statistical significance (p=0.04) in its
primary endpoint over the first 6-week double-blind treatment cycle
(Cycle 1) (available here). The study enrolled 169 patients
randomized 2:1 to receive either SGX301 or placebo in Cycle
1. After the subsequent additional 6-week treatment in the
open-label Cycle 2, the response rate in patients receiving a total
of 12 weeks treatment increased two and a half-fold (40% with
p<0.0001 compared to placebo and p<0.0001 compared to 6-weeks
treatment). These highly statistically significant results
confirm the benefit of continued SGX301 treatment in CTCL patients
(press release available here). Treatment responses were
assessed at Week 8 (after 6 weeks of treatment) and at Week 16
(after 12 weeks of treatment). A positive response was
defined as an improvement of at least 50% in the CAILS for three
index lesions evaluated. Further analysis of the patients
receiving SGX301 through 12 weeks has revealed that treatment of
both patch and plaque lesions was equally effective. Similar
to the overall findings, the responses of individual lesions were
statistically significantly improved after 12 weeks treatment
relative to 6 weeks treatment with SGX301 or placebo.
Importantly, this improvement was seen equally for both patches
(response 37%, p=0.0009) and plaques (response 42%, p<0.0001), a
differentiating feature of SGX301 relative to other treatment
modalities in CTCL.
Cycle 3 of the study was designed as a compassionate use,
optional, cycle where patients could elect to continue SGX301
treatment for an additional 6 weeks (up to a total of 18 weeks) for
all their lesions. Sixty-six percent (66%) of patients
elected to continue into Cycle 3. During this cycle, SGX301
was applied to multiple cancerous skin lesions on the body,
maximizing the exposure to the drug. Including Cycle 3 in the
study enabled a more rigorous safety assessment in the context of
extended and increased exposure to SGX301. Similar to the
overall findings, the responses of individual lesions after three
cycles of treatment with SGX301 was statistically significant after
Cycle 3 relative to outcomes after Cycles 1 and 2 (49% of all
lesions responded with a CAILS score reduction of at least 50%,
with a statistically significant change from end of Cycle 2
[p=0.0009] and compared to patients receiving placebo only in Cycle
1 [p<0.0001]). Further, no synthetic hypericin was
detected in the bloodstream of patients, minimizing safety concerns
of drug effects outside of the tumor area. All safety data
continues to indicate that SGX301 treatment is safe and well
tolerated, in marked contrast to other available second-line and
off-label therapies for CTCL.
About Cutaneous T-Cell Lymphoma (CTCL)
CTCL is a class of non-Hodgkin's lymphoma (NHL), a type of
cancer of the white blood cells that are an integral part of the
immune system. Unlike most NHLs which generally involve
B-cell lymphocytes (involved in producing antibodies), CTCL is
caused by an expansion of malignant T-cell lymphocytes (involved in
cell-mediated immunity) normally programmed to migrate to the
skin. These malignant cells migrate to the skin where they
form various lesions, typically beginning as patches that may
progress to more difficult to treat raised plaques and
tumors. Mortality is related to the stage of CTCL, with
median survival generally ranging from about 12 years in the early
stages to only 2.5 years when the disease has advanced. There is
currently no cure for CTCL and no FDA approved first-line treatment
option. Typically, CTCL lesions are treated and regress but
usually return either in the same part of the body or in new
areas.
CTCL constitutes a rare group of NHLs, occurring in about 4% of
the approximate 700,000 individuals living with the disease.
It is estimated, based upon review of historic published studies
and reports and an interpolation of data on the incidence of CTCL
that it affects over 25,000 individuals in the US, with
approximately 3,000 new cases seen annually.
About SGX301
SGX301 is a novel first-in-class photodynamic therapy utilizing
safe visible light for activation. The active ingredient in
SGX301 is synthetic hypericin, a potent photosensitizer that is
topically applied to skin lesions, is taken up by the malignant
T-cells, and then activated by fluorescent light 16 to 24 hours
later. The use of visible light in the red-yellow spectrum
has the advantage of penetrating more deeply into the skin (much
more so than ultraviolet light) and therefore potentially treating
deeper skin disease and thicker lesions. This treatment approach
avoids the risk of secondary malignancies (including melanoma)
inherent with the frequently employed DNA-damaging drugs and other
phototherapy that are dependent on ultraviolet exposure.
Combined with photoactivation, hypericin has demonstrated
significant anti-proliferative effects on activated normal human
lymphoid cells and inhibited growth of malignant T-cells isolated
from CTCL patients. In a published Phase 2 clinical study in
CTCL, patients experienced a statistically significant (p=0.04)
improvement with topical hypericin treatment whereas the placebo
was ineffective. SGX301 has received orphan drug and fast
track designations from the FDA, as well as orphan designation from
the European Medicines Agency (EMA).
The Phase 3 FLASH trial enrolled a total of 169 patients (166
evaluable) with Stage IA, IB or IIA CTCL. The trial consists of
three treatment cycles. Treatments were administered twice weekly
for the first 6 weeks and treatment response was determined at the
end of the 8th week of each cycle. In the first double-blind
treatment cycle, 116 patients received SGX301 treatment (0.25%
synthetic hypericin) and 50 received placebo treatment of their
index lesions. A total of 16% of the patients receiving SGX301
achieved at least a 50% reduction in their lesions (graded using a
standard measurement of dermatologic lesions, the CAILS score)
compared to only 4% of patients in the placebo group at 8 weeks
(p=0.04) during the first treatment cycle (primary endpoint).
SGX301 treatment in the first cycle was safe and well
tolerated.
In the second open-label treatment cycle (Cycle 2), all patients
received SGX301 treatment of their index lesions. Evaluation of 155
patients in this cycle (110 receiving 12 weeks of SGX301 treatment
and 45 receiving 6 weeks of placebo treatment followed by 6 weeks
of SGX301 treatment), demonstrated that the response rate among the
12-week treatment group was 40% (p<0.0001 vs the placebo
treatment rate in Cycle 1). Comparison of the 12-week and 6-week
treatment groups also revealed a statistically significant
improvement (p<0.0001) between the two groups, indicating that
continued treatment results in better outcomes. SGX301
continued to be safe and well tolerated. Additional analyses also
indicated that SGX301 is equally effective in treating both plaque
(response 42%, p<0.0001 relative to placebo treatment in Cycle
1) and patch (response 37%, p=0.0009 relative to placebo treatment
in Cycle 1) lesions of CTCL, a particularly relevant finding given
the historical difficulty in treating plaque lesions in
particular.
The third (optional) treatment cycle (Cycle 3) was focused on
safety and all patients could elect to receive SGX301 treatment of
all their lesions. Of note, 66% of patients elected to continue
with this optional compassionate use / safety cycle of the study.
Of the subset of patients that received SGX301 throughout all 3
cycles of treatment, 49% of them demonstrated a treatment response
(p<0.0001 vs patients receiving placebo in Cycle 1). Moreover,
in a subset of patients evaluated in this cycle, it was
demonstrated that SGX301 is not systemically available, consistent
with the general safety of this topical product observed to date.
At the end of Cycle 3, SGX301 continued to be well tolerated
despite extended and increased use of the product to treat multiple
lesions. Follow-up visits are expected to be completed in
2020.
Overall safety of SGX301 is a critical attribute of this
treatment and was monitored throughout the three treatment cycles
(Cycles 1, 2 and 3) and the 6-month follow-up period.
SGX301's mechanism of action is not associated with DNA damage,
making it a safer alternative than currently available therapies,
all of which are associated with significant and sometimes fatal,
side effects. Predominantly these include the risk of
melanoma and other malignancies, as well as the risk of significant
skin damage and premature skin aging. Currently available
treatments are only approved in the context of previous treatment
failure with other modalities and there is no approved front-line
therapy available. Within this landscape, treatment of CTCL
is strongly motivated by the safety risk of each product.
SGX301 potentially represents the safest available efficacious
treatment for CTCL. With no systemic absorption, a compound
that is not mutagenic and a light source that is not carcinogenic,
there is no evidence to date of any potential safety
issues.
The Phase 3 CTCL clinical study was partially funded by the
National Cancer Institute via a Phase II SBIR grant
(#1R44CA210848-01A1) awarded to Soligenix, Inc.
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 Specialized
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 Public Health Solutions business segment includes active
development programs for RiVax®, our ricin toxin vaccine
candidate, SGX943, our therapeutic candidate for antibiotic
resistant and emerging infectious disease, and our research
programs to identify and develop novel vaccine candidates targeting
viral infection including Ebola, Marburg and SARS-CoV-2 (the cause
of COVID-19). 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), the Defense Threat Reduction Agents (DTRA) 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. 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, such as
experienced with the COVID-19 outbreak. 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, or any of
our other clinical/preclinical trials. Despite the
statistically significant result achieved in the SGX301 Phase 3
clinical trial for the treatment of cutaneous T-cell lymphoma,
there can be no assurance that a marketing authorization from the
FDA or EMA will be successful. Further, there can be no
assurance that RiVax® will qualify for a biodefense
Priority Review Voucher (PRV) or that the prior sales of PRVs will
be indicative of any potential sales price for a PRV for
RiVax®. Also, no assurance can be provided that the
Company will receive or continue to receive non-dilutive government
funding from grants and contracts that have been or may be awarded
or for which the Company will apply in the future. 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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