Soligenix, Inc. has commenced patient enrollment in its confirmatory Phase 3 clinical trial, FLASH2, evaluating HyBryte (synthetic hypericin) for the treatment of cutaneous T-cell lymphoma (CTCL). This randomized, double-blind, placebo-controlled, multi-center study aims to enroll approximately 80 patients with early-stage CTCL in the U.S. and Europe. The trial design replicates the successful elements of the first Phase 3 FLASH study, but extends the treatment period to 18 weeks of continuous treatment, with the primary efficacy assessment occurring at the end of this extended period.
HyBryte: A Novel Photodynamic Therapy
HyBryte (SGX301) is a first-in-class photodynamic therapy that uses safe, visible light for activation. The active ingredient, synthetic hypericin, is a potent photosensitizer applied topically to skin lesions. Malignant T-cells take up hypericin, which is then activated by visible light approximately 24 hours later. This approach offers the advantage of deeper skin penetration compared to ultraviolet light and avoids the risk of secondary malignancies associated with DNA-damaging drugs and other UV-dependent phototherapies.
FLASH2 Trial Design and Objectives
The FLASH2 trial is designed to confirm the efficacy and safety of HyBryte observed in the previous Phase 3 FLASH study. Key design components from the first FLASH study, including the primary endpoint and inclusion/exclusion criteria, remain the same. The primary endpoint is the reduction in the modified Composite Assessment of Index Lesion Severity (mCAILS) score. By extending the treatment duration to 18 weeks, the FLASH2 trial aims to demonstrate HyBryte's effect over a more prolonged, "real-world" treatment course.
In the first Phase 3 study, patients completing 18 weeks of HyBryte therapy showed a 49% treatment response rate (p<0.0001 vs. placebo). The extended treatment duration in FLASH2 is expected to statistically validate HyBryte's increased effect over a longer period.
Expert Commentary
"In the Phase 3 FLASH study, HyBryte was shown to be efficacious in early stage CTCL with a promising safety profile," stated Ellen Kim, MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, Professor of Dermatology at the Hospital of the University of Pennsylvania, and Lead Investigator of the FLASH2 study. "CTCL patients are often searching for alternative treatments, with limited options especially for early-stage disease. HyBryte offers a distinct treatment option which patients found extremely useful and continue to specifically request. We look forward to demonstrating the expanded positive impact of the use of HyBryte in a more 'real world' setting with 18-weeks of continuous treatment in this 80-patient study."
Addressing Unmet Needs in CTCL Treatment
CTCL is a rare form of non-Hodgkin's lymphoma affecting T-cell lymphocytes, with an estimated 31,000 individuals affected in the U.S. and 38,000 in Europe. Currently, there is no cure for CTCL, and available treatments often have significant side effects, including the risk of melanoma and other malignancies. HyBryte's mechanism of action, which is not associated with DNA damage, makes it a potentially safer alternative.
Anticipated Milestones
An interim analysis of the FLASH2 study is anticipated in early 2026. Soligenix plans to provide periodic updates on the trial's progress throughout 2025.
Additional Studies Supporting HyBryte
An open-label, investigator-initiated study evaluating extended HyBryte treatment for up to 12 months in early-stage CTCL patients has shown promising results. An interim update showed that over 70% of patients (5 of 6 who completed at least 18 weeks of therapy) achieved "Treatment Success," defined as a ≥50% improvement in the mCAILS score. Three of these successes were achieved within the first 12 weeks, with two patients achieving a complete response by 18 weeks. The study is supported by a $2.6 million FDA Orphan Products Development grant.
