Phase 3 clinical study of
HyBryte™ in CTCL initiating in 2024
PRINCETON, N.J., Nov. 19,
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 the formation of a European Medical Advisory Board (MAB) to
provide additional medical/clinical strategic guidance to the
Company as it advances its confirmatory Phase 3 multicenter,
double-blind, 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 (U.S.) 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.
"Stemming from the positive feedback from the European Medicines
Agency (EMA) on the key design components of our confirmatory Phase
3 placebo-controlled study evaluating the safety and efficacy of
HyBryte™, we consider expert European involvement a necessary
component for the development of this program. As such, it is an
honor to have such a prestigious and dedicated group of clinicians
and leaders in the field committed to working with us as we develop
HyBryte™," stated Christopher J.
Schaber, PhD, President and Chief Executive Officer of
Soligenix. "We have assembled some of the leading CTCL experts, who
collectively have the experience of treating thousands of patients
with this rare condition, and complement the strong CTCL MAB we've
established in the U.S. The support of these European experts is a
further testament to the opportunity HyBryte™ could provide for
patients suffering from this disease worldwide."
Comprised of internationally renowned physicians with extensive
experience in treating and running clinical research trials in
CTCL, this esteemed MAB will play an important advisory role in the
conduct and interpretation of the upcoming Phase 3 clinical study
and the associated regulatory interactions with health authorities.
The MAB will provide feedback, input, and guidance on clinical
strategies and their implementation, as well as on other critical
items, such as health economics and reimbursement, to assist
Soligenix in meeting the needs of patients suffering from CTCL.
European MAB Members
Martine Bagot, MD, PhD –
France
Martine Bagot is Professor and
Head of the Department of Dermatology at the Hôpital Saint Louis in Paris, France and co-directs the INSERM Unit
976 Human Immunology, Pathophysiology and Immunotherapy. Dr. Bagot
also chairs the French Group for the Study of Cutaneous Lymphomas.
Dr. Bagot has co-authored more than 750 peer-reviewed publications,
most of which are in the complementary fields of dermatology,
immunology, and oncology. Main publications include numerous
clinical trials in dermato-oncology. Dr. Bagot is involved with
major European international societies such as the International
Society for Cutaneous Lymphoma (ISCL), The European Society for
Dermatological Research (ESDR), and the European Organisation for
Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task
Force, where she previously served as its President and is
currently a steering committee member.
Pietro Quaglino, MD –
Italy
Pietro Quaglino is Associate
Professor of Dermatology at the Department of Medical Sciences,
University of Turin Medical School, Italy. His clinical and research activities
focus on melanoma, cutaneous lymphoma, and immune dermatology. He
is the principal investigator of several clinical trials in
melanoma and cutaneous lymphoma. He is board member of the GIPMe
(Gruppo Italiano Polidisciplinare sul Melanoma), board member and
treasurer of the IMI (Italian Melanoma Intergroup), past chairman
and current steering committee member of the EORTC Cutaneous
Lymphoma Task Force, and member of the Board Directors of the ISCL.
He has published more than 160 peer-reviewed scientific papers. Dr.
Quaglino is Assistant Editor of the Giornale Italiano di
Dermatologia e Venereologia, reviewer of international journals on
dermatology and referee for ANVUR (National Agency for the
Evaluation of Universities and Research Institutes).
Pablo Luis Ortiz-Romero,
MD, PhD – Spain
Pablo Luis Ortiz-Romero is
Professor of Dermatology and Head of the Dermatology Department at
Hospital Universitario 12 de Octubre, Spain. He is a distinguished dermatologist and
researcher specializing in cutaneous lymphomas, particularly
mycosis fungoides and Sézary syndrome forms of CTCL. His experience
is extensive, having contributed to over 200 publications and
numerous clinical studies in the field. Dr. Ortiz-Romero is
affiliated with the ISCL and has served on its Board of Directors.
His research includes innovative treatments for CTCL, and he is one
of the leading physicians focused on novel treatments for CTCL in
Spain. He served as the Secretary
General of the EORTC Cutaneous Lymphoma Tumor Group and is
currently a member of its steering committee.
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
treatment 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 significant 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) and a more
aggressive titration of the light doses 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. Additional supportive studies
have demonstrated the utility of longer treatment times (Study
RW-HPN-MF-01), the lack of significant systemic exposure to
hypericin after topical application (Study HPN-CTCL-02) and its
relative efficacy and tolerability compared to Valchlor®
(Study HPN-CTCL-04).
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, 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'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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