Published Results Confirm and Extend
Response Results from Phase 3 FLASH Study
PRINCETON, N.J., May 16, 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 the
results of its compatibility study evaluating HyBryte™ (synthetic
hypericin) for the treatment of cutaneous T-cell lymphoma (CTCL)
have been published in the Journal of the European Academy of
Dermatology & Venereology (JEADV) Clinical Practice. The
publication highlights the positive clinical results from study,
HPN-CTCL-02, evaluating HyBryte™ in the treatment of CTCL.
The open-label study enrolled 9 patients to receive 8 weeks of
HyBryte™ treatment of their cancerous lesions, with an assessment
of treatment response conducted at week 10 using the modified
Composite Assessment of Index Lesion Severity (mCAILS) score. The
treatment response results of 22% following 8 weeks of twice
weekly HyBryte™ therapy reinforces and confirms the results of
the Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin)
trial published in the Journal of the American Medical
Association (JAMA) Dermatology, despite the fact that patients
in Study HPN-CTCL-02 were specifically selected to have more
extensive disease consistent with its potential commercial use.
Additionally, in this study all patients had improvements in their
cumulative mCAILS score (average improvement of 36.4%, range 8 to
100%). Results in individual lesions showed that 7 of the 27 index
lesions (25.9%) had at least a 50% improvement in their mCAILS
score and 4 of the 27 index lesions (14.8%) were completely
resolved after as little as 8 weeks of treatment. Other key
evaluations included measurements of systemic exposure and
electrocardiograms, which yielded extremely low and limited levels
of systemic hypericin (plateau concentration of approximately
0.00013 μg/mL) detected in the blood and no observable impact to
normal sinus rhythm, reinforcing the safety of HyBryte™.
"Being able to share the important results of this clinical
trial with the world through publication in JEADV is a privilege
and highlights the clinical significance of our work with
HyBryte™," stated Brian Poligone,
MD, PhD, Director of the Rochester Skin Lymphoma Medical Group,
Fairport, NY, and Principal
Investigator for the compatibility study and Leading Enrolling
Investigator in the FLASH study. "I have seen firsthand the promise
this therapy can offer patients and was happy to build upon our
knowledge working with HyBryte™ in a clinical setting reflective of
real-world use. The ease at which photodynamic therapy with
HyBryte™ is conducted and the outstanding safety profile we
continue to see as demonstrated by the systemic exposure and
cardiac results reviewed in this paper makes me very excited for
its potential future clinical use. I look forward to participating
in the confirmatory Phase 3 FLASH2 study later this year."
About JEADV
The Journal of the European Academy of Dermatology and
Venereology (JEADV) is a peer reviewed journal that publishes
articles of general and practical interest in the field of
dermatology and venereology including clinical and basic science
topics, as well as research with practical implications. It does so
through editorials, review and practice articles, original papers
of general interest, short reports, letters to the editor, features
and EADV announcements. JEADV has an extensive international
readership with over 2 million downloads every year.
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 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.
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 will be 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 United States 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
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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. 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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