Soligenix, Inc. has successfully completed the transfer of synthetic hypericin manufacturing from Europe to the United States through its partnership with Sterling Pharma Solutions, marking a critical milestone in advancing its rare disease treatment programs. The transfer includes optimization and implementation of a commercially viable, scalable production process for the active ingredient used in topical drug formulations HyBryte™ and SGX302.
Manufacturing Partnership Enables Commercial Scale Production
The collaboration with Sterling Pharma Solutions has established current good manufacturing practice (cGMP) production capabilities for clinical trials, with plans for a long-term commercial manufacturing partnership. Sterling's expertise in active pharmaceutical ingredient manufacturing, including innovative continuous flow chemistry solutions, will support process refinement and cost reduction efforts.
"We are pleased to have successfully produced larger quantities of cGMP synthetic hypericin, and look forward to continuing to work with Sterling to refine the process for process validation while further reducing our cost of goods," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix.
Adam Kujath, Site Head at Sterling Pharma Solutions' Germantown, Wisconsin facility, emphasized the partnership's value: "Sterling is pleased to be collaborating with Soligenix on this important program. We believe that Sterling's expertise in active pharmaceutical ingredient manufacturing, including developing innovative solutions such as continuous flow chemistry for this product, will continue to provide great value to the Soligenix program while we work towards a commercial supply agreement."
HyBryte™ Shows Promise in Cutaneous T-Cell Lymphoma Treatment
HyBryte™ (SGX301) represents a novel, first-in-class photodynamic therapy utilizing safe, visible light for activation. The treatment involves topical application of synthetic hypericin, a potent photosensitizer that is taken up by malignant T-cells and activated by visible light approximately 24 hours later. This approach uses red-yellow spectrum light that penetrates more deeply into skin compared to ultraviolet light, potentially treating deeper skin disease and thicker lesions.
The therapy's mechanism avoids DNA damage, distinguishing it from currently available treatments that carry risks of secondary malignancies including melanoma, significant skin damage, and premature aging. HyBryte™ has received orphan drug and fast track designations from the FDA, as well as orphan designation from the European Medicines Agency.
Phase 3 Clinical Trial Results Demonstrate Efficacy
The published Phase 3 FLASH trial enrolled 169 patients (166 evaluable) with Stage IA, IB or IIA cutaneous T-cell lymphoma across three treatment cycles. In the first double-blind treatment cycle, 116 patients received HyBryte™ treatment (0.25% synthetic hypericin) while 50 received placebo treatment.
Results showed 16% of patients receiving HyBryte™ achieved at least a 50% reduction in their lesions compared to only 4% of patients in the placebo group at 8 weeks (p=0.04). The treatment was safe and well tolerated throughout the study period.
In the second open-label cycle, evaluation of 155 patients demonstrated a 40% response rate among the 12-week treatment group (p<0.0001 versus placebo treatment rate in Cycle 1). Additional analyses indicated HyBryte™ is equally effective in treating both plaque lesions (42% response, p<0.0001) and patch lesions (37% response, p=0.0009), addressing the historical difficulty in treating plaque lesions.
The optional third cycle focused on safety, with 66% of patients electing to continue treatment. Among patients receiving HyBryte™ throughout all three cycles, 49% demonstrated positive treatment response (p<0.0001 versus patients receiving placebo in Cycle 1).
Regulatory Path Forward and Second Phase 3 Trial
Following the first Phase 3 study, both the FDA and EMA indicated they would require a second successful Phase 3 trial to support marketing approval. The confirmatory study, called FLASH2, is expected to initiate before the end of 2024 with EMA agreement on key design components.
FLASH2 is designed as a randomized, double-blind, placebo-controlled, multicenter study enrolling approximately 80 subjects with early-stage CTCL. The study extends the double-blind, placebo-controlled assessment to 18 weeks of continuous treatment, with the primary endpoint assessment occurring at the 18-week timepoint.
The FDA has expressed preference for a longer duration comparative study over a placebo-controlled trial, and discussions continue on potential modifications to the development path. The University of Pennsylvania received a $2.6 million FDA Orphan Products Development grant over four years to support investigator-initiated studies evaluating HyBryte™ for expanded treatment in early-stage CTCL patients, including home use settings.
Addressing Significant Unmet Medical Need
Cutaneous T-cell lymphoma represents a rare group of non-Hodgkin's lymphomas, occurring in approximately 4% of the more than 1.7 million individuals living with the disease in the U.S. and Europe. The condition affects an estimated 31,000 individuals in the U.S. with approximately 3,200 new cases annually, and 38,000 individuals in Europe with approximately 3,800 new cases annually.
CTCL is caused by expansion of malignant T-cell lymphocytes that migrate to the skin, forming lesions that typically begin as patches and may progress to raised plaques and tumors. Median survival ranges from about 12 years in early stages to only 2.5 years when advanced. Currently, no cure exists for CTCL, and available treatments are only approved following previous treatment failures, with no approved front-line therapy available.
The manufacturing transfer completion positions Soligenix to advance its clinical programs toward potential commercialization, addressing a significant unmet medical need in rare skin cancers where treatment options remain limited and carry substantial safety risks.
