FDA Clears Soligenix's Synthetic Hypericin for Phase 2 Clinical Trial in Psoriasis

Visible light-activated synthetic hypericin is a novel, first-in-class, photodynamic therapy (PDT) that is expected to avoid much of the long-term risks associated with other PDT treatments.

The U.S. Food and Drug Administration (FDA) has cleared Soligenix’s Investigational New Drug (IND) application for a Phase 2a clinical trial of topically-applied SGX302 (synthetic hypericin).

Patient enrollment is slated to begin in the fourth quarter of 2022.

"During the last year, we have made announcements of important development milestones that we have achieved with HyBryte (synthetic hypericin) in the treatment of early stage cutaneous T-cell lymphoma (CTCL),” says Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix, in a news release. “We have clearly validated synthetic hypericin's biologic activity with the Phase 3 FLASH study in this orphan disease, where we expect to file a New Drug Application (NDA) in the second half of 2022.  We are excited to expand synthetic hypericin's development into different cutaneous T-cell diseases such as psoriasis, as a component of our long-term strategy to enhance the value of this unique compound.  Psoriasis is an ongoing unmet medical need, with as many as 7.5 million people in the U.S. and 60-125 million people worldwide affected by this incurable disease. Given our promising results with hypericin to date, including a small Phase 1/2 proof of concept clinical trial in mild-to-moderate psoriasis, we are hopeful synthetic hypericin will have a role to play in helping patients suffering from this difficult to treat and chronic disease."

Under this IND, the Phase 2a clinical trial of SGX302 will be a randomized, double-blind, placebo-controlled study that will enroll up to 32 patients aged 18 years or older with mild to moderate, stable psoriasis covering 2 to 30% of their body.  Patients will receive placebo or SGX302 (randomized 1:1) as a twice weekly treatment for up to 18 weeks. Each treatment will consist of the application of SGX302 followed approximately 24 hours later with visible light activation. Efficacy endpoints will include the extent of lesion clearance and patient reported quality of life indices.

Visible light-activated synthetic hypericin is a novel, first-in-class, photodynamic therapy (PDT) that is expected to avoid much of the long-term risks associated with other PDT treatments.  Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions and taken up by cutaneous T-cells. With subsequent activation by safe, visible light, T-cell apoptosis is induced, addressing the root cause of psoriasis lesions. Other PDTs have shown efficacy in psoriasis with a similar apoptotic mechanism, albeit using ultraviolet (UV) light associated with more severe potential long-term safety concerns.  The use of visible light in the red-yellow spectrum has the advantage of deeper penetration into the skin (much more than UV light) potentially treating deeper skin disease and thicker plaques and lesions, similar to what was observed in the positive Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study in CTCL.  Synthetic hypericin or HyBryte™ (tradename used in CTCL) was demonstrated in this study to be equally effective in treating both plaque (42% treatment response rate after 12 weeks treatment, p<0.0001 relative to placebo treatment) and patch (37%, p=0.0009) lesions in this orphan disease caused by malignant T-cells.  In a published Phase 1/2 proof of concept clinical study using synthetic hypericin, efficacy was demonstrated in patients with CTCL (58.3% response, p=0.04) as well as psoriasis (80% response, p<0.02).

This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with both the frequently used DNA-damaging drugs and other phototherapies that are dependent on UV A or B exposure.  The use of synthetic hypericin coupled with safe, visible light also avoids the risk of serious infections and cancer associated with the systemic immunosuppressive treatments used in psoriasis. 

The Phase 3 FLASH trial enrolled a total of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The trial consisted of three treatment cycles. Treatments were administered twice weekly in 6-week cycles. In the first double-blind treatment cycle, 116 patients received HyBryte™ treatment and 50 received placebo treatment of their index lesions. A total of 16 percemt of the patients receiving HyBryte™ achieved at least a 50 percent reduction in their lesions (using the standard Composite Assessment of Index Lesions Severity [CAILS] score) compared to only 4 percent of patients in the placebo group after just 6 weeks of treatment (p=0.04). Further treatment with HyBryte™ increased the number of treatment successes to 40 percent and 49 percent after 12 and 18 weeks, respectively (p<0.0001 for both). Additional analyses also indicated that HyBryte is equally effective in treating both plaque (42% treatment response rate after 12 weeks treatment, p<0.0001 relative to placebo treatment in Cycle 1) and patch (37%, p=0.0009) lesions of CTCL, a particularly relevant finding given the historical difficulty in treating plaque lesions. This is also relevant to psoriasis where the lesions can be thicker than the patches observed in CTCL.

In a subset of patients evaluated during their third treatment cycle, it was demonstrated that HyBryte™ is not systemically available, consistent with the general safety of this topical product observed to date. At the end of Cycle 3, HyBryte continued to be well tolerated despite extended and increased use of the product to treat multiple lesions.