Soligenix discontinued HyBryte development after its Phase 3 FLASH2 trial was halted for futility following an interim efficacy analysis in cutaneous T-cell lymphoma.
Written by: Kirti Kumbhar, M. Pharm (QA)
Reviewed by: Pharmacally Editorial Team
Soligenix has discontinued development of HyBryte™ (synthetic hypericin) for cutaneous T-cell lymphoma (CTCL) after its confirmatory Phase 3 FLASH2 trial was recommended for termination due to futility. The decision followed an interim efficacy analysis conducted in April 2026, which did not show the expected efficacy signal after 18 weeks of continuous treatment. Soligenix’s Board of Directors subsequently terminated the program on June 11, 2026.
CTCL and HyBryte
CTCL is a rare form of non-Hodgkin lymphoma arising from malignant T cells that primarily involve the skin. Lesions can develop from patches to plaques and tumors, with prognosis varying substantially by disease stage.
HyBryte, also known as SGX301, is a topical photodynamic therapy based on synthetic hypericin. The treatment was designed to apply the photosensitizer directly to affected skin, followed approximately 24 hours later by exposure to visible red-yellow light to activate it. Unlike ultraviolet-based phototherapy, HyBryte uses visible light.
HyBryte had received FDA orphan drug and fast track designations and EMA orphan designation.
Regulatory History and FLASH2 Design
Soligenix submitted an NDA for HyBryte to the FDA on December 14, 2022. The FDA issued a Refusal to File letter in February 2023, determining that the application was not sufficiently complete for substantive review. Following discussions with the agency, the FDA required positive results from a second Phase 3 study in addition to the earlier FLASH trial.
FLASH2 was designed as a randomized, double-blind, placebo-controlled, multicenter confirmatory Phase 3 study. Unlike the original FLASH trial, which used three six-week treatment cycles separated by breaks, FLASH2 evaluated 18 weeks of continuous treatment.
FLASH2 Interim Findings
The Data Monitoring Committee recommended stopping FLASH2 (NCT06470451) for futility after the interim efficacy analysis. Soligenix did not disclose detailed numerical efficacy results from the interim analysis, but said the clinical signal observed in the earlier FLASH study was not reproduced after 18 weeks of continuous treatment.
The earlier FLASH Phase 3 study had shown a statistically significant response at eight weeks, with 16% of HyBryte-treated patients achieving at least a 50% reduction in lesions compared with 4% receiving placebo (p=0.04). Response increased with extended treatment, reaching 40% at 12 weeks and 49% among patients who completed all three treatment cycles.
Safety and Program Termination
Soligenix reported that prespecified safety evaluations in FLASH2 showed a good safety profile. However, the absence of sufficient efficacy led the company to discontinue further development.
Following its June 11 decision, Soligenix said it would orderly wind down FLASH2 and related HyBryte activities, with approximately $70,000 in expected close-out and related costs.
Path Forward
Christopher J. Schaber, PhD, President and CEO of Soligenix, said the discontinuation of HyBryte did not diminish the company’s broader pipeline or strategic value. He highlighted the continued advancement of SGX945 (dusquetide) for Behçet’s disease, which demonstrated promising preliminary efficacy and was generally safe and well tolerated in a Phase 2 study, as well as the company’s ThermoVax® heat-stable vaccine platform.
Reference
Soligenix Announces Recent Updates and Second Quarter 2026 Financial Results – Aug 7, 2026
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.