Continuous Synthetic Hypericin Generates Responses in Early-Stage Cutaneous T-Cell Lymphoma

Early-Stage CTCL | Image Credit:

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Treatment with synthetic hypericin (HyBryte) for up to 12 months produced responses in patients with early-stage cutaneous T-cell lymphoma (CTCL), according to interim data from the investigator-initiated phase 2 RW-HPN-MF-01 trial (NCT05872854) announced by Soligenix.¹

Findings showed that among evaluable patients who completed at least 18 weeks of therapy (n = 6), over 70% achieved treatment success, which was defined as an improvement of at least 50% in cumulative modified Composite Assessment of Index Lesion Severity (mCAILS) score vs baseline. Among the 5 patients to experience treatment success, 3 reached this end point within the first 12 weeks of therapy, including 2 patients who achieved a complete response (CR).

A total of 9 patients had been enrolled and treated at the time of this analysis. Two patients had recently started the study, and 2 patients dropped out due to logistical reasons. One patient who withdrew from the study experienced an mCAILS improvement of more than 30% at week 18.

“The CR rate, consistent treatment response and safety profile across multiple clinical studies to date with [synthetic hypericin] has been exciting to see," Ellen Kim, MD, principal investigator of the RW-HPN-MF-01 trial, director of the Penn Cutaneous Lymphoma Program, vice chair of Clinical Operations in the Dermatology Department, and professor of dermatology at the Hospital of the University of Pennsylvania, stated in a news release. "In the first phase 3 FLASH study [NCT02448381], [synthetic hypericin] was shown to be efficacious with a benign safety profile compared to the current therapies of steroids, chemotherapeutics and ultraviolet light in this chronic orphan disease. With limited treatment options, especially in the early stages of their disease, [patients with] CTCL are often searching for alternative treatments. In our US FDA–funded study, initial results evaluating the expanded use of [synthetic hypericin] in a ‘real-world’ treatment setting remain very promising, further supporting and extending results from the previous positive phase 2 and 3 clinical trials. We look forward to continuing to work with the FDA to complete this study while we participate in the confirmatory phase 3 placebo-controlled FLASH2 study [NCT06470451].”

Prior data from the FLASH trial showed at least a 50% reduction in CAILS score at 8 weeks in 16% of patients treated with synthetic hypericin (n = 116) compared with 4% for placebo (n = 50; P = .04).

However, in February 2023, the FDA issued a refusal to file letter for a new drug application (NDA) seeking the approval of synthetic hypericin for the treatment of patients with early-stage CTCL.² The NDA was supported by data from FLASH.

Both the FDA and the European Medicines Agency previously indicated that they would require a second successful phase 3 trial to support marketing approval of synthetic hypericin, and the agent is being further evaluated in the randomized FLASH2 study.¹

The investigator-initiated RW-HPN-MF-01 trial was designed to assess continuous treatment with synthetic hypericin for up to 12 months.³ The ongoing study is enrolling patients at least 18 years of age with stage IA, IB, or 2A mycosis fungoides CTCL. Key exclusion criteria consist of treatment with steroids or other topical treatments on CTCL lesions within 2 weeks of enrollment; electron beam irradiation within 3 months of enrollment; and a history of significant systemic immunosuppression.

All enrolled patients are receiving synthetic hypericin, which is applied to CTCL lesions and treated with visible light 24 hours (±6) later starting at 5 J/cm² twice per week at least 2 days apart for up to 54 weeks.

Improvement in mCAILS score is the trial’s primary end point.^1,3 Secondary end points include CR rate in all lesions; the proportion of patients with a Physician Global Assessment score of 3; the proportion of patients to achieve at least a 50% improvement in Modified Severity Weighted Assessment Tool score; changes in CAILS score in each lesion; pharmacokinetics; and safety.³

Data from the interim analysis of the investigator-initiated trial also showed that synthetic hypericin was safe and well tolerated.¹

“We are pleased with these recent study results and that the FDA is continuing to financially support the [synthetic hypericin] program, giving patients an opportunity to access the therapy in an open-label setting," Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, added in a news release. "CTCL is an incredibly difficult to treat orphan disease and remains an area of unmet medical need with a very limited number of safe and effective treatment options. Following the initial phase 3 FLASH study, which demonstrated the safety and efficacy of shorter courses of [synthetic hypericin] therapy, we are pleased to see that continuing treatment for longer time periods is resulting in the anticipated improved outcomes for patients. As the body of compelling data continues to grow in support of this novel therapy, we look forward to continuing to work with Dr Kim on this important study as well as advancing enrollment in the 80-patient confirmatory phase 3 FLASH2 replication study. We will plan to provide additional updates on the investigator-initiated study as data become available.”

References

1. HyBryte™ expanded treatment continues to demonstrate positive outcomes in early-stage cutaneous T-cell lymphoma. News release. Soligenix. January 14, 2025. Accessed January 14, 2025. https://ir.soligenix.com/2025-01-14-HyBryte-TM-Expanded-Treatment-Continues-to-Demonstrate-Positive-Outcomes-in-Early-Stage-Cutaneous-T-Cell-Lymphoma
2. Soligenix receives refusal to file letter from US FDA for HyBryte new drug application in the treatment of cutaneous T-cell lymphoma. Soligenix. News release. February 14, 2023. Accessed January 14, 2025. https://ir.soligenix.com/2023-02-14-Soligenix-Receives-Refusal-to-File-Letter-from-U-S-FDA-for-HyBryte-TM-New-Drug-Application-in-the-Treatment-of-Cutaneous-T-Cell-Lymphoma
3. Treatment of mycosis fungoides with hypericin ointment and visible light (RW-HPN-MF-01). ClinicalTrials.gov. Updated July 29, 2025. Accessed January 14, 2025. https://clinicaltrials.gov/study/NCT05872854