Significant Efficacy against Plaque Lesions
Also Demonstrated with HyBryte™
PRINCETON, N.J., Dec. 2, 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 analysis
of the post-treatment data from the open-label study (protocol
HPN-CTCL-04) comparing HyBryte™ (synthetic hypericin) to
Valchlor® (mechlorethamine) has demonstrated continued
improvement in HyBryte™ treated patients and their individual
lesions even after stopping treatment. The study, which enrolled 10
patients randomized 1:1 with 12 weeks of treatment and 4 weeks of
follow-up post-treatment, was previously reported to demonstrate a
positive difference in the overall per patient treatment response
rate (60% in the HyBryte™ group vs. 20% in the Valchlor®
group) at the end of treatment. After the 4-week follow-up period
(Week 16), the majority (3 of 5) of HyBryte™ patients continued to
demonstrate improvement with at least a further 10% improvement
(absolute difference) at Week 16 relative to the primary outcome
measure at Week 12, including one of the HyBryte™ patients
achieving a "complete response". In contrast, of the four patients
that completed the Valchlor® arm of the study, none
achieved this level of improvement by Week 16. For patients, a
treatment response was defined as a ≥50% improvement in their
cumulative mCAILS (modified Composite Assessment of Index Lesion
Severity) score over 3 to 5 lesions. Treatment response was also
assessed on individual lesions. There was a similar continued
improvement in the lesion responses over time, with the plaque
lesions of particular interest given their increasing association
with risk of overall disease progression and long-term mortality.
At the 12-week (end of treatment) timepoint, the HyBryte™ treated
plaque lesions were statistically significantly improved compared
to the Valchlor® treated plaques (63%, [10/16] treatment
success with HyBryte™ vs. 17%, [2/12] with Valchlor®,
p=0.02). By Week 16, the response rates in lesions treated with
HyBryte™ were statistically significant responses for all lesions
(72% HyBryte™ vs 28% Valchlor®, p=0.02) and specifically
for plaque lesions (75% responding plaque lesions with HyBryte™
treatment vs. 17% with Valchlor®, p=0.006) relative to
the Valchlor® group. No safety concerns with HyBryte™
were raised during the follow-up period.
"Following the positive results from the previous Phase 2 and 3
studies where we previously participated in evaluating HyBryte™, we
were excited to support Soligenix's effort to conduct a prospective
comparative assessment of HyBryte™ versus
Valchlor®," stated Dr. Brian
Poligone, Director of the Rochester Skin Lymphoma Medical
Group, and Principal Investigator for the comparability study.
"Despite the small study sample size and a randomization that
resulted in the HyBryte™ group having patients with more
extensive disease, HyBryte™ continues to demonstrate its rapid
onset of action and benign safety profile, compared to one of the
most widely prescribed approved drugs for early-stage CTCL. The
potentially enhanced effect on plaque lesions mirrors the promising
activity against very difficult to treat lesions, such
as refractory folliculotropic lesions, which we also observed
in the first Phase 3 study. We look forward to continuing our
support of Soligenix in the development of HyBryte™ by
participating in the upcoming confirmatory Phase 3
placebo-controlled study."
"These results support the positive HyBryte™ data from the
previously completed Phase 3 FLASH study and demonstrates that a
relatively short treatment period with the drug can result in
clinically meaningful outcomes," stated Christopher J. Schaber, PhD, President and Chief
Executive Officer of Soligenix. "This relatively rapid response to
HyBryte™ therapy fits nicely into the treatment arsenal for
CTCL and reinforces the relative safety of HyBryte™ in these
patients compared to other therapies currently in use. We look
forward to continuing to work with Dr. Poligone and all of our
committed clinical investigators to initiate the 80-patient
confirmatory Phase 3 replication study (FLASH2) next month."
The purpose of the HPN-CTCL-04 study was to obtain preliminary
comparative assessment of the safety and efficacy of
Valchlor® versus HyBryte™ following 12 weeks of
treatment as measured in 3 to 5 prospectively identified index
lesions for each patient. HyBryte™ was administered twice weekly
with light exposure approximately 24 hours after drug application,
while Valchlor® was applied as often as daily as per the
package insert. At the end of the 12-week treatment period, 60% of
the HyBryte™ patients met the prospectively defined level of
"Treatment Success" (≥50% improvement in their cumulative mCAILS
score compared to Baseline) compared to only 20% of the
Valchlor® patients; although due to the small sample
size the results do not achieve statistical significance. Of the
remaining two HyBryte™ patients that did not achieve treatment
success, both saw a substantial (≥30%) reduction in their mCAILS
score. In contrast, in the Valchlor® group, of the
remaining 4 patients that did not achieve treatment success, one
worsened and dropped from the study, one improved less than 30% and
two improved ≥30%. The average cumulative improvement in mCAILS at
12 weeks was 52.5% in the HyBryte™ patients versus 34.7% in the
Valchlor® patients. HyBryte™ was well tolerated in all
patients whereas 1 of the 5 patients receiving Valchlor®
had to be withdrawn from the trial because of a clinically
significant allergic contact dermatitis from
Valchlor®.
During the 4-week follow-up period (Week 16) the majority (3 of
5) of HyBryte™ patients continued to demonstrate lesion improvement
with at least a further 10% reduction (absolute difference) at Week
16 relative to the primary outcome measure at Week 12, including
one of these patients achieving a "complete response". The
remaining two HyBryte™ subjects showed either a modest (<5%)
decrease or increase relative to their primary endpoint response at
Week 12. In contrast, of the four patients that completed the
Valchlor® arm of the study, one worsened (>15%
change), one had a modest decrease, one remained static, and one
had a modest improvement by Week 16. Analysis of the individual
lesion responses showed similar response profiles, with treatment
response observed in 61% of HyBryte™ treated lesions vs. 33%
response in Valchlor® treated lesions (p=0.18) at Week
12. The lesions responses increased over the 4 weeks following
treatment to 72% responding lesions with HyBryte™ treatment and
decreased over the 4 weeks following treatment to 28% with
Valchlor, p=0.02. Focusing specifically on the plaque lesions, 63%
of HyBryte™ treated plaque lesions (10/16) responded to treatment
vs. 17% of Valchlor® treated plaque lesions (2/12;
p=0.02). Again, the responses of the HyBryte™ treated lesions
increased over the 4 weeks following treatment to 75% responding
plaque lesions with HyBryte™ treatment and the Valchlor®
treated lesions response rate was unchanged at 17%, p=0.006. Plaque
lesions have been acknowledged as both more difficult to treat and,
more recently, as potentially linked to disease progression. The
link with disease progression was most recently reported at the
European Organisation for Research and Treatment of Cancer (EORTC)
Cutaneous Lymphoma Tumour Group Annual Meeting in Lausanne,
Switzerland on October 9-11, 2024.
When comparing the tolerance of the topical therapies (i.e.,
reactions where the drug was applied to the skin) in this trial, it
is notable that all patients tolerated HyBryte™ well and had no
adverse events "Related" to the therapy. In contrast, 60% of the
Valchlor® treated patients had at least one adverse
event "Related" to the therapy. These adverse events in the
Valchlor® group included rashes, application site
sensitivity, allergic contact dermatitis, and dermatitis, with one
patient requiring steroid treatment, one requiring temporary
interruption of Valchlor® treatments, and one requiring
permanent discontinuation of Valchlor®. No such
instances were reported in the HyBryte™ group.
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 U.S. Food and Drug Administration (FDA), as well as orphan
designation from the European Medicines Agency (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 responses also revealed a statistically
significant improvement (p<0.0001) between the two timepoints,
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.
Following the first Phase 3 study of HyBryte™ for the treatment
of CTCL, the FDA and the EMA indicated that they would require a
second successful Phase 3 trial to support marketing approval. With
agreement from the EMA on the key design components, the second,
confirmatory study, called FLASH2, is expected to be initiated
before the end of 2024. This study is a randomized, double-blind,
placebo-controlled, multicenter study that will enroll
approximately 80 subjects with early-stage CTCL. The FLASH2 study
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, this 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. Given the
extensive engagement with the CTCL community, the esteemed Medical
Advisory Board and the previous trial experience with this disease,
accelerated enrollment in support of this study is anticipated,
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, this study is being initiated. At the same time,
discussions with the FDA will continue on potential modifications
to the development path to adequately address their feedback.
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 1.7 million individuals living with the disease in
the U.S. and Europe (European
Union and United Kingdom). 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 31,000 individuals in the U.S. (based on
SEER data, with approximately 3,200 new cases seen annually) and
approximately 38,000 individuals in Europe (based on ECIS prevalence estimates,
with approximately 3,800 new cases annually).
About Soligenix
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's current expectations about its future results,
performance, prospects and opportunities, including but not limited
to, potential market sizes, patient populations, clinical trial
enrollment, the expected timing for closing the offering described
herein and the intended use of proceeds therefrom. 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. Additionally, despite the biologic activity
observed in aphthous ulcers induced by chemotherapy and radiation,
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, 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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