Positive Clinical Results from HyBryte™ Compatibility Study in the Treatment of Cutaneous T-Cell Lymphoma Published in JEADV Clinical Practice

Rhea-AI Summary

Soligenix announced positive results from its HyBryte™ compatibility study for treating cutaneous T-cell lymphoma (CTCL), published in JEADV Clinical Practice. The study, HPN-CTCL-02, enrolled 9 patients, revealing a 22% treatment response rate after 8 weeks of HyBryte™ therapy. The results align with the Phase 3 FLASH trial, showing an average improvement of 36.4% in cumulative mCAILS scores. Key metrics included low systemic hypericin levels and no adverse effects on cardiac rhythm, confirming HyBryte™'s safety. The study points to the potential real-world use of HyBryte™ and precedes a confirmatory Phase 3 FLASH2 study.

Positive

• The compatibility study showed a 22% treatment response rate after 8 weeks of HyBryte™ therapy.
• Patients in the study had an average improvement of 36.4% in their cumulative mCAILS score.
• Seven of 27 index lesions showed at least a 50% improvement in mCAILS score, and 14.8% of lesions were completely resolved.
• Low systemic hypericin levels (0.00013 μg/mL) indicated minimal systemic exposure.
• No adverse effects on normal sinus rhythm were observed, highlighting HyBryte™'s safety.
• The study results align with the previous Phase 3 FLASH trial, reinforcing their validity.
• The publication in JEADV Clinical Practice underscores the clinical significance of the findings.

Negative

• The open-label study enrolled only 9 patients, which may limit the generalizability of the results.
• The treatment response rate of 22% might be considered moderate compared to other therapies.

Insights

Medical Research Analyst

The recently published study results for HyBryte™ are significant for Soligenix, particularly in the context of treating cutaneous T-cell lymphoma (CTCL), a rare form of skin cancer. The study reinforced the findings from the earlier Phase 3 FLASH trial, showing a 22% treatment response rate following 8 weeks of therapy. Importantly, the study also demonstrated a 36.4% average improvement in cumulative lesion severity scores, with 25.9% of lesions showing at least a 50% improvement and 14.8% completely resolving. This indicates a strong efficacy profile for HyBryte™, which is important given the unmet medical need in CTCL treatment.

Additionally, the study's safety profile was favorable, with minimal systemic exposure and no significant cardiac effects. This is particularly noteworthy as safety concerns can often be a major barrier to the adoption of new therapies. The low systemic hypericin levels and absence of cardiac rhythm issues suggest that HyBryte™ could be a safer alternative to existing treatments.

From a retail investor's perspective, these results are quite promising as they not only validate the efficacy and safety of HyBryte™ but also pave the way for its potential commercialization. Given that the study subjects had more extensive disease, the positive results bolster confidence in the drug's real-world applicability and market potential.

Financial Analyst

The clinical success of HyBryte™ could significantly impact Soligenix's financial outlook. Positive clinical data often lead to increased investor confidence, potential partnerships and can expedite regulatory approvals. The publication of these results in a reputable journal like JEADV adds to the credibility and visibility of HyBryte™, which could drive up the stock price due to renewed investor interest.

In the short term, we might see a positive stock price movement as the market reacts to the news. In the long term, if HyBryte™ receives regulatory approval and is successfully commercialized, it could generate substantial revenue for Soligenix. With CTCL being a rare disease, treatments like HyBryte™ can often obtain orphan drug status, which includes benefits like market exclusivity and potential tax credits, further enhancing the drug's financial prospects.

Investors should also consider the ongoing and future studies, such as the confirmatory Phase 3 FLASH2 study. Positive outcomes from these studies could further validate HyBryte™ and increase Soligenix's market valuation. However, it's essential to keep an eye on the competitive landscape and the regulatory hurdles that might arise.

Oncology Doctor

From a clinical standpoint, the results presented for HyBryte™ in treating cutaneous T-cell lymphoma are encouraging. CTCL is a challenging disease to manage and the availability of effective and safe treatment options is limited. The significant reduction in lesion severity and the complete resolution observed in some cases suggest that HyBryte™ could become an important tool in the therapeutic arsenal against CTCL.

One of the standout aspects of HyBryte™ is its excellent safety profile. The minimal systemic exposure and lack of adverse cardiac effects are particularly reassuring, as they suggest that the therapy could be suitable for a broad range of patients, including those who might be at higher risk of side effects from other treatments. This could lead to better patient compliance and outcomes.

For investors, this means there's a high likelihood that HyBryte™ could be well-received by both the medical community and patients, translating into strong market uptake upon approval. The involvement of experienced investigators and the rigorous nature of the study further enhance the credibility of these findings.

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 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. 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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SOURCE SOLIGENIX, INC.

FAQ

What were the results of Soligenix's HyBryte™ study for CTCL?

The study showed a 22% treatment response rate after 8 weeks, with an average improvement of 36.4% in cumulative mCAILS scores.

What is HyBryte™?

HyBryte™ is a synthetic hypericin-based therapy developed by Soligenix for treating cutaneous T-cell lymphoma (CTCL).

How many patients were enrolled in the HyBryte™ study?

The HyBryte™ compatibility study enrolled 9 patients.

What was the systemic exposure level of hypericin in the HyBryte™ study?

The study reported extremely low systemic hypericin levels, with a plateau concentration of approximately 0.00013 μg/mL.

Did the HyBryte™ study show any cardiac adverse effects?

No adverse effects on normal sinus rhythm were observed in the study.

How do the HyBryte™ study results compare with the Phase 3 FLASH trial?

The HyBryte™ study results are consistent with the Phase 3 FLASH trial, reinforcing the effectiveness and safety of the therapy.

What is the next step for HyBryte™ development?

Soligenix plans to conduct a confirmatory Phase 3 FLASH2 study to further validate HyBryte™ for real-world use.