HyBryte Has an Acceptable Safety Profile in Cutaneous T-Cell Lymphoma

Treatment with HyBryte (SGX301) has an acceptable safety profile and is not associated with safety concerns in patients with cutaneous T-cell lymphoma (CTCL), according to a meeting of the Data Monitoring Committee (DMC) for the ongoing phase 3 FLASH2 study (NCT06470451).¹

The safety profile of HyBryte is consistent with the safety data reported in all prior clinical studies of this agent.

“In the phase 3 FLASH study, HyBryte was shown to be efficacious in early-stage CTCL with a promising safety profile,” Ellen Kim, MD, director of the Penn Cutaneous Lymphoma Program, vice chair of Clinical Operations in the Dermatology Department, and a professor of dermatology at the Hospital of the University of Pennsylvania in Philadelphia, as well as the lead investigator of the FLASH2 study, stated in a news release. “[Patients with] CTCL are often searching for alternative treatments, with limited options, especially for early-stage disease. HyBryte offers a distinct treatment option, including both a benign [adverse] effect profile and potentially rapid response rates, which patients found extremely useful and continue to specifically request. We look forward to continuing to enroll patients into FLASH2 to further elucidate the positive impact of HyBryte in a more ‘real world’ setting with 18 weeks of continuous treatment in this 80-patient pivotal study.”

The FLASH2 enrollment update is on track to be announced in the fourth quarter of 2025. The DMC also plans to conduct a prespecified blinded interim efficacy analysis of the trial in the first half of 2026.

“We are pleased to have reached this important milestone, confirming the expected safety to date in the confirmatory FLASH2 study,” Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, the developer of HyBryte, added in the news release. “As patient enrollment continues to track with our initial estimates, we anticipate providing an update, including enrollment progress and the blinded aggregate response rate, before year-end. We look forward to completing this study on schedule with topline results [reported] in the second half of 2026.”

What Is the Mechanism of Action of HyBryte?

HyBryte is a novel, first-in-class photodynamic therapy. It contains the active ingredient synthetic hypericin, which is a photosensitizer that is applied topically to skin lesions, absorbed by malignant T cells, and activated by safe, visible light that penetrates the skin more deeply than ultraviolet light. This gives HyBryte the potential to treat deep skin disease, as well as thick lesions and plaques. Furthermore, since HyBryte conducts limited systemic absorption, is not mutagenic, and is activated by a light source that is not carcinogenic, its mechanism of action is not associated with DNA damage, unlike currently available therapies.

What Was the Rationale for Conducting the FLASH2 Study of HyBryte in Patients With CTCL?

FLASH2 is a confirmatory study that builds on data from the previously reported phase 3 FLASH study (NCT02448381), in which the overall response rate (ORR) was 49% in evaluable patients with stage IA, IB, or IIA CTCL who received HyBryte for 18 weeks, a statistically significant improvement over the ORR among evaluable patients who received placebo during cycle 1 (P < .0001).

FLASH2 also builds on findings from the comparative phase 2 HPN-CTCL-04 study (NCT06149247) of HyBryte that showed its favorable efficacy and tolerability profiles compared with those of mechlorethamine gel (Valchlor) in patients with CTCL.² Additionally, FLASH2 builds on the ongoing phase 2, investigator-initiated RW-HPN-MF-01 study (NCT05872854) of HyBryte in patients with early-stage CTCL, which showed that treatment with HyBryte induced an ORR of 75% after 18 weeks of treatment.³

What Is the Design of the FLASH2 Study of HyBryte in Patients With CTCL?

The randomized, double-blind, placebo-controlled, multicenter FLASH2 study is enrolling approximately 80 patients with early-stage CTCL.^1,4 Patients must have at least 3 evaluable, discrete lesions.⁴

Patients are randomly assigned to receive continuous treatment with HyBryte with a 0.25% hypericin concentration for 18 weeks, or continuous placebo, with no treatment breaks between cycles as were included in the design of the FLASH trial.^1,4

In FLASH2, the primary end point analysis will occur at the end of the 18 weeks of treatment.¹ The primary end point is the number of patients with a treatment response per the Modified Composite Assessment of Index Lesion Disease Severity score.⁴ Secondary end points include patch lesion response rate and plaque lesion response rate.

References

1. Soligenix achieves important safety milestone in its confirmatory phase 3 clinical trial of HyBryte for the treatment of cutaneous T-cell lymphoma. News release. Solgenix, Inc. October 7, 2025. Accessed October 7, 2025. https://ir.soligenix.com/2025-10-07-Soligenix-Achieves-Important-Safety-Milestone-in-its-Confirmatory-Phase-3-Clinical-Trial-of-HyBryte-TM-for-the-Treatment-of-Cutaneous-T-Cell-Lymphoma
2. Soligenix announces positive clinical results from a comparative study evaluating HyBryte against Valchlor in the treatment of cutaneous T-cell lymphoma.News release. Solgenix, Inc. June 25, 2024. Accessed October 7, 2025. https://ir.soligenix.com/2024-06-25-Soligenix-Announces-Positive-Clinical-Results-from-a-Comparative-Study-Evaluating-HyBryte-TM-Against-Valchlor-R-in-the-Treatment-of-Cutaneous-T-Cell-Lymphoma
3. Positive outcome in 75% of CTCL patients treated with HyBryte for 18 weeks.News release. Solgenix, Inc. April 14, 2025. Accessed October 7, 2025. https://ir.soligenix.com/2025-04-14-Positive-Outcome-in-75-of-CTCL-Patients-Treated-with-HyBryte-TM-for-18-Weeks
4. Confirmatory study of topical HyBryte vs. placebo for the treatment of CTCL (FLASH2). ClinicalTrials.gov. Updated July 31, 2025. Accessed October 7, 2025. https://clinicaltrials.gov/study/NCT06470451