Broad Efficacy and Improved Safety Profile of HyBryte™ Presented at Society for Investigative Dermatology Virtual Meeting

On May 4, 2021 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, reported that Ellen Kim, MD, Medical Director, Dermatology Clinic, Perelman Center for Advanced Medicine, Professor of Dermatology at the Hospital of the University of Pennsylvania, and the Lead Principal Investigator for the Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study, presented confirmatory data at the Society for Investigative Dermatology (SID) Virtual Meeting, held May 3-8, 2021 (Press release, Soligenix, MAY 4, 2021, View Source [SID1234579044]). The presentation was selected to be shown during a Concurrent Mini-Symposium for Patient-Targeted Research. The presented data demonstrated the ability of HyBryte (SGX301) to treat both patch and plaque disease, including generating complete disease responses, while being associated with fewer and less severe adverse events than other currently approved skin-directed therapies for cutaneous T-cell lymphoma (CTCL).

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Oral Presentation:

Topical hypericin ointment photodynamic therapy is effective and safe in CTCL (FLASH study) Dr. Kim’s presentation is archived on the SID Virtual Meeting site and will be accessible via registration until May 31, 2021. The abstract is available here and attendees can register to see the presentation here.

Key Highlights:

HyBryte is activated by visible light at a wavelength of 500-650 nm, which provides deeper dermal penetration than ultraviolet (UV) spectrum light. This resulted in statistically significant clinical responses observed in patches as well as deeper plaque lesions, which are typically more difficult to treat and generally less responsive to UV light therapy.
In addition to its demonstrated, statistically significant efficacy which ultimately led to 49% of patients achieving at least a 50% reduction in their lesions (graded using a standard measurement of dermatologic lesions, the CAILS score) after 18 weeks of therapy (p<0.0001), complete responses of all treated index lesions were also shown to occur. These complete responses increased in frequency as treatment with HyBryte continued and photographs demonstrating this response were reviewed.
Compared to other, second-line, approved drugs for the treatment of CTCL, HyBryte demonstrated significantly less safety concerns. This was reflected in the low rate of study discontinuation attributed to adverse events which showed only a 5% overall drop-out rate during the treatment phase in HyBryte treated patients, lower than typically observed in other early stage CTCL trials.
"Additional CTCL therapies with fewer and less severe side effects are desperately needed in our field," noted Dr. Kim. "I believe the efficacy and safety we saw HyBryte demonstrate in this trial proves that it can help us fill that need. This study was the largest multicenter, randomized, double-blind, placebo-controlled skin directed therapy study in MF/CTCL (mycosis fungoides/cutaneous T-cell lymphoma) to date and I would like to thank all site investigators, and especially our patients, for their contributions to developing this promising new therapy."

About the Society for Investigative Dermatology Virtual Meeting

The SID meeting is an annual meeting, dedicated to a broad range of dermatology related topics, as described here. SID’s mission is to advance the sciences relevant to skin diseases through education, advocacy and scholarly exchange of scientific information.

About HyBryte

HyBryte (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 visible light 16 to 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 European Medicines Agency (EMA).

The Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) 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, 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 the first 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 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. Follow-up visits were completed in Q4 2020, and the clinical study report to support the NDA is in the process of being finalized.

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 no 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 CTCL clinical study was partially funded by the National Cancer Institute via a Phase II SBIR grant (#1R44CA210848-01A1) awarded to Soligenix, Inc.