Randomized Study with 18 Weeks Continuous
Treatment Expected to Replicate and Extend Results from the First,
Statistically Significant Phase 3 Study
PRINCETON, N.J., April 3,
2024 /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
it has received agreement from the European Medicines Agency (EMA)
on the key design components of a confirmatory Phase 3
placebo-controlled study evaluating the safety and efficacy of
HyBryte™ (synthetic hypericin) in the treatment of cutaneous T-cell
lymphoma (CTCL) patients with early-stage disease. This
confirmatory 18-week study is expected to enroll approximately 80
patients in the United States and
Europe and is targeted to begin
patient enrollment by the end of 2024 with top-line results
anticipated in the second half of 2026.
The confirmatory study, called FLASH2 (Fluorescent Light
Activated Synthetic Hypericin 2), replicates the double-blind,
placebo-controlled design used in the first successful Phase 3
FLASH study that consisted of three 6-week treatment cycles (18
weeks total), with the primary efficacy assessment occurring at the
end of the initial 6 week double-blind, placebo-controlled
treatment cycle (Cycle 1). However, the second study extends the
double-blind, placebo-controlled assessment to 18 weeks of
continuous treatment (no "between-Cycle" treatment breaks) with the
primary endpoint assessment occurring at the end of the 18-week
timepoint. In the first Phase 3 study, a treatment response of 49%
(p<0.0001 vs patients receiving placebo in Cycle 1) was observed
in patients completing 18 weeks (3 cycles) of therapy. In this
second study, all important clinical study design components remain
the same as in the first FLASH study, including the primary
endpoint and key inclusion-exclusion criteria. The extended
treatment for a continuous 18 weeks in a single cycle is expected
to statistically demonstrate HyBryte's™ increased effect over a
more prolonged, "real world" treatment course.
"In treating CTCL, which is a chronic cancer with no cure,
long-term safety is a strong driver of treatment choice. Most
current treatment options for CTCL are associated with significant
safety concerns, including black-box warnings," stated Brian Poligone, MD, PhD, Director of the
Rochester Skin Lymphoma Medical Group, Fairport, NY. "Clinical
studies with HyBryte™ have demonstrated strong and rapid efficacy
with a very benign safety profile, with broad applicability across
different lesion types, different skin tones and different disease
stages. I know I can speak for my colleagues that have been
involved with these studies when I say that the data generated to
date has been extremely compelling. This second study is very
similar to the first FLASH study, and should build on these
compelling data, while allowing us to more closely treat as we
would in a 'real world' setting. We believe the outcome of this
trial will further validate the utility of HyBryte™ in early-stage
CTCL and we look forward to participating in this important
study."
"With its chronic course and major impact on patient quality of
life, CTCL is an orphan disease in urgent need of additional
treatment options that are well-tolerated and safe over the long
term," stated Christopher Schaber,
PhD, President and Chief Executive Officer of Soligenix. "Studies
to date have indicated a substantial increase in efficacy with
longer treatment and similar performance against both patch and
plaque lesions. These results are derived from one of the largest
studies ever conducted in CTCL, and we believe this second study
will both substantiate and improve upon these results. Given our
extensive engagement with the CTCL community, our esteemed Medical
Advisory Board and our previous trial experience with this disease,
we anticipate being able to accelerate enrollment in support of
this study, including the potential to enroll previously identified
and treated HyBryte™ patients from the FLASH study. Discussions
with the FDA on an appropriate study design remain ongoing. While
collaborative, the agency has expressed a preference for a longer
duration comparative study over a placebo-controlled trial. Given
the shorter time to potential commercial revenue and the similar
trial design to the first FLASH study afforded by the EMA
accepted protocol, we will initiate that study. At the same time,
we will continue discussions with the FDA on modifying the
development path to adequately address their feedback."
The confirmatory Phase 3, randomized, double-blind,
placebo-controlled, multicenter study includes approximately 80
subjects with early-stage CTCL. It will evaluate the efficacy and
safety of HyBryte™ topically applied to CTCL lesions twice weekly
for 18 weeks, with each application followed 21 (±3) hours later by
the administration of safe, visible light at a wavelength of 500 to
650 nm. The light will be administered starting at 6
J/cm2 twice weekly. This will be increased upwards by 2
J/cm2 until: 1) the patient experiences a Grade 1
erythema, 2) the patient reaches the maximum dose of 30
J/cm2, or 3) the patient cannot tolerate the treatment
time, whichever comes first. All of the patient's lesions that are
readily available for exposure to the visible light source will be
treated and 3 to 5 index lesions in each patient will be
prospectively identified and indexed for the modified composite
assessment of index lesions severity (mCAILS) evaluation prior to
randomization (baseline). The primary efficacy endpoint will be
assessed on the percent of patients in each of the two treatment
groups (i.e., HyBryte™ and placebo) achieving a Partial or Complete
Response (yes/no) of the treated lesions defined as a ≥ 50%
reduction in the total mCAILS score for the 3-5 index lesions
following 18 weeks of treatment compared to the total mCAILS score
at baseline. Other secondary measures will assess treatment
response (including duration), degree of improvement, time to
relapse and safety. Following treatment, all patients will be
followed every 4 weeks for a total of 12 weeks (through Week 30).
The Data Monitoring Committee (DMC) will conduct one (1) interim
analysis when approximately 60% of the total subjects have
completed the primary endpoint evaluation. The primary efficacy
endpoint and the key safety endpoints will be analyzed. A sample
size recalculation may be performed after examining the assumptions
or the trial halted for either futility, safety concerns, or
overwhelming efficacy. Soligenix, participating clinical
investigators, and any personnel involved in trial conduct will
remain blinded to study treatment until completion of the
trial.
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
safe, 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 EMA.
The 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 (Cycle 1), 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 this 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 FLASH 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 the
University of Pennsylvania 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 more than 1.2 million 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 approximately 30,000 individuals in the U.S. (based on
SEER data, with approximately 3,200 new cases seen annually) and
over 20,000 individuals in Europe
(based on 5-year prevalence data, with approximately 5,600 new
cases 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 sodium) as a novel photodynamic therapy utilizing safe
visible light for the treatment of cutaneous T-cell lymphoma
(CTCL). With successful completion of the second Phase 3 study,
regulatory approvals will be sought to support potential
commercialization worldwide. 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
(SGX945) in Behçet's Disease.
Our Public Health Solutions business segment includes
development programs for RiVax®, our ricin toxin vaccine
candidate, as well as 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, and include the
expected amount and use of proceeds from the offering and the
expected closing date of the offering. 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 first HyBryte™ (SGX301) Phase 3 clinical trial for the
treatment of cutaneous T-cell lymphoma, there can be no assurance
that the second HyBryte™ (SGX301) Phase 3 clinical trial will be
successful or that a marketing authorization from the FDA or EMA
will be granted. Additionally, although the EMA has agreed to the
key design components of the second HyBryte™ (SGX301) Phase 3
clinical trial, no assurance can be given that the Company will be
able to modify the development path to adequately address the FDA's
concerns or that the FDA will not require a longer duration
comparative study. Notwithstanding the result in the first HyBryte™
(SGX301) Phase 3 clinical trial for the treatment of cutaneous
T-cell lymphoma and the Phase 2a 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. Despite the positive efficacy results demonstrated in
the Phase 2 and 3 clinical studies of SGX942 for the treatment of
oral mucositis due to chemoradiation therapy for head and neck
cancer, there can be no assurance as to the timing or success of
the clinical trials of SGX945 for the treatment of Behçet's
Disease. 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 (the "SEC"), including, but not
limited to, the Company's preliminary prospectus (Registration No.
333-271049) filed with the SEC on May 4,
2023, and 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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