Soligenix intends to seek guidance from the
FDA on how to further advance
HyBryte™ towards potential
approval
PRINCETON, N.J., Feb. 14,
2023 /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
the United States (U.S.) Food and
Drug Administration (FDA) has provided the Company with a Refusal
to File (RTF) letter for its HyBryte™ (synthetic hypericin) new
drug application (NDA) in the treatment of early stage cutaneous
T-cell lymphoma (CTCL), a rare cancer and area of unmet
medical need affecting over 25,000 patients in the U.S.
Upon preliminary review, the FDA determined that the NDA,
submitted on December 14, 2022, was
not sufficiently complete to permit substantive review. Soligenix
first learned of the RTF decision via this letter and is reviewing
its contents to determine the appropriate next steps, which
includes, but is not limited to, requesting a Type A meeting with
the FDA to clarify and respond to the issues identified in the
letter and to seek additional guidance concerning information that
the agency would require for a resubmitted NDA to be deemed
acceptable to file.
"We are fully determined to work with the FDA staff as quickly
as possible to better understand the open issues and clarify the
potential path to successfully resubmitting our application,"
stated Christopher J. Schaber, PhD, President and Chief
Executive Officer of Soligenix. "We remain focused on
advancing HyBryte™ as a potential new first-in-class treatment
option for the CTCL community of patients, families and healthcare
professionals."
About HyBryte™
HyBryte™ (research name SGX301) is a novel, first-in-class,
photodynamic therapy utilizing safe, visible light for
activation. The active ingredient in HyBryte™ is synthetic
hypericin, a potent photosensitizer that is topically applied to
skin lesions that is taken up by the malignant T-cells, and then
activated by visible light approximately 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 plaques and 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. HyBryte™ has received orphan drug and fast
track designations from the FDA, as well as orphan designation from
the European Medicines Agency (EMA).
The recently published Phase 3 FLASH trial enrolled a total
of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The
trial consisted 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
HyBryte™ treatment (0.25% synthetic hypericin) and 50 received
placebo treatment of their index lesions. A total of 16% of the
patients receiving HyBryte™ 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). HyBryte™ treatment in the first cycle was safe
and well tolerated.
In the second open-label treatment cycle (Cycle 2), all patients
received HyBryte™ treatment of their index lesions. Evaluation of
155 patients in this cycle (110 receiving 12 weeks of HyBryte™
treatment and 45 receiving 6 weeks of placebo treatment followed by
6 weeks of HyBryte™ 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. HyBryte™
continued to be safe and well tolerated. Additional analyses also
indicated that HyBryte™ 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 HyBryte™ 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 HyBryte™ throughout all 3
cycles of treatment, 49% of them demonstrated a positive 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 HyBryte™ is not systemically available,
consistent with the general safety of this topical product observed
to date. At the end of Cycle 3, HyBryte™ continued to be well
tolerated despite extended and increased use of the product to
treat multiple lesions.
Overall safety of HyBryte™ 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.
HyBryte'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.
HyBryte™ potentially represents the safest available efficacious
treatment for CTCL. With very limited 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. In addition,
the FDA awarded an Orphan Products Development grant to support the
evaluation of HyBryte™ for expanded treatment in patients with
early-stage CTCL, including in the home use setting. The
grant, totaling $2.6 million over 4
years, was awarded to a prestigious academic institution that was a
leading enroller in the Phase 3 FLASH study.
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 and may
progress to 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.
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 U.S., with
approximately 3,000 new cases seen annually.
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 and moving toward
potential commercialization of HyBryte™ (SGX301 or synthetic
hypericin) as a novel photodynamic therapy utilizing safe visible
light for the treatment of cutaneous T-cell lymphoma (CTCL). With a
successful Phase 3 study completed, regulatory approval is being
sought and commercialization activities for this product candidate
are being advanced initially in the U.S. Development programs in
this business segment also include expansion of synthetic hypericin
(SGX302) into psoriasis, our first-in-class innate defense
regulator (IDR) technology, dusquetide (SGX942) for the treatment
of inflammatory diseases, including 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).
Our Public Health Solutions business segment includes active
development programs for RiVax®, our ricin toxin vaccine
candidate, and SGX943, our therapeutic candidate for antibiotic
resistant and emerging infectious disease, and our vaccine programs
targeting filoviruses (such as Marburg and Ebola) and CiVax™, our
vaccine candidate for the prevention of COVID-19 (caused by
SARS-CoV-2). 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 Agency (DTRA) and the Biomedical Advanced
Research and Development Authority (BARDA).
For further information regarding Soligenix, Inc., please visit
the Company's website at https://www.soligenix.com and
follow us on LinkedIn and Twitter at @Soligenix_Inc.
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 U.S. 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 U.S. 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 any of its clinical/preclinical trials.
Despite the statistically significant result achieved in the
HyBryte™ (SGX301) Phase 3 clinical trial for the treatment of
cutaneous T-cell lymphoma and the FDA's acceptance of the NDA for
HyBryte™, there can be no assurance that a marketing authorization
from the FDA or EMA will be successful. Notwithstanding the result
in the HyBryte™ (SGX301) Phase 3 clinical trial for the treatment
of cutaneous T-cell lymphoma and the Phase 1/2 proof-of-concept
clinical trial of SGX302 for the treatment of psoriasis, there can
be no assurance as to the timing or success of the clinical trials
of SGX302 for the treatment of psoriasis. 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. HyBryte™
potential market information is a forward-looking statement, and
investors are urged not to place undue reliance on this
information. While the Company has determined this potential market
size based on assumptions that its believes are reasonable, there
are a number of factors that could cause expectations to change or
not be realized. 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.