(changes are in Time New Roman font) Cutaneous T-cell lymphoma (CTCL) is a rare form of Non-Hodgkin's Lymphoma (NHL) affecting approximately 21,000 patients annually in the United States and can be characterized by either an indolent or aggressive disease progression. Either case is accompanied by significant morbidity, particularly due to the skin effects of the disease. The indolent disease may eventually progress to a more aggressive systemic disease associated with significant mortality. When the disease is primarily localized to the skin it is referred to as mycosis fungoides (MF) and is characterized by abnormal accumulation of T-cells in the skin, causing lesions, which increasingly cover the body as the disease progresses. These lesions can be scaly patches of varying color and/or eczema like-rashes and/or psoriasis-like rashes. Thick tumors may develop on the skin that may eventually become open, infected ulcers. The lesions are often associated with severe itching, making sleep and other daily activities difficult. Early treatment of MF can prevent progression to the open ulcerative skin tumor stage. CTCL is an orphan disease with no approved first-line therapy. The active pharmaceutical ingredient of Soligenix's SGX301 technology is synthetic hypericin, a photo-activated agent that intracellularly concentrates in the endoplasmic reticulum and, with activation by visible light, generates singlet oxygen that causes localized reactive-oxygen species that initiates the mitochondrial apoptotic pathway Because of its lack of DNA interactions and negative Ames test, it is anticipated that this treatment will have a substantially lower risk for secondary cancer development than the majority of CTCL treatments that, because their anti-tumor effects are generated through DNA damage mechanisms, have either theoretical or proven long-term association with secondary cancers including melanoma. Importantly, hypericin is not by itself mutagenic, like other treatments, and is activated by visible light, which is not carcinogenic. The two components can be easily combined at the site of a skin lesion, resulting in highly selective delivery and killing of tumor cells with minimal systemic impact on the patient. Phase 1 and 2 clinical studies have clearly demonstrated its safety and efficacy, including a patient response rate >50% with hypericin treatment (0.1% or 0.25%). SGX301 has been granted Fast Track Designation by the US FDA for the first line treatment of CTCL and hypericin has been granted Orphan Product Designation for the treatment of CTCL (Designation #99-1310). This proposal seeks to conduct a Phase 3 registration trial, HPN-CTCL-01, evaluating the safety and efficacy of 0.25% hypericin in the treatment of CTCL.
The Specific Aims of this proposal are: 1) Test the hypothesis that in patients with early stage cutaneous T-cell Lymphoma (CTCL), topically applied hypericin in association with standard fluorescent bulb light phototherapy given twice per week for 6 weeks can induce a clinically meaningful improvement in skin lesions when compared to placebo therapy; and 2) Assess the utility of repeat treatments of hypericin in early stage CTCL.
(changes are in Time New Roman font) In the United States, there are approximately 2,500-3,000 new cases per year and 20,500 people living with cutaneous T-cell lymphoma (CTCL), a relatively rare form of Non-Hodgkin's Lymphoma (NHL), and there is currently no FDA approved cure or first line treatment for early stage CTCL (i.e., mycosis fungoides or MF). The primary objective of the Soligenix SGX301 development program, including the Phase 3 clinical Study HPN- CTCL-01, which is the subject of this application, is to demonstrate the safety and efficacy of SGX301 (0.25% synthetic hypericin) in the treatment of MF. SGX301 is a novel first-in-class photodynamic therapy utilizing safe visible light for activation, and has received Orphan Product and Fast Track designation from the FDA. The Soligenix approach has a high probability of commercialization of a therapeutic to treat an important and neglected orphan disease with no approved first-line therapy.