HPN-CTCL-02 Study of SGX301 Shows Promise in CTCL

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Positive clinical results were observed among patients with cutaneous T-cell lymphoma (CTCL) treated with SGX301 (HyBryte; synthetic hypericin) as part of the open-label HPN-CTCL-02 study (NCT05380635).¹

Nine patients were enrolled in the study and treated with SGX301 for 8 weeks. An assessment of treatment response was then conducted at week 10 using the modified Composite Assessment of Index Lesion Severity (mCAILS) score. According to findings published in the Journal of the European Academy of Dermatology & Venereology (JEADV) Clinical Practice, following 8 weeks of twice weekly SGX301, the treatment response rate was 22%.²

These data reinforce the positive results of the phase 3 FLASH trial (NCT02448381), which were previously published in the Journal of the American Medical Association (JAMA) Dermatology. Here, topical synthetic hypericin activated with visible light was found to be effective and well-tolerated in patients with early-stage mycosis fungoides CTCL.³

Notably, the patients included in Study HPN-CTCL-02 were specifically selected to have more extensive disease consistent with its potential commercial use.

"Being able to share the important results of this clinical trial with the world through publication in JEADV is a privilege and highlights the clinical significance of our work with [SGX301]," stated Brian Poligone, MD, PhD, director of the Rochester Skin Lymphoma Medical Group, Fairport, NY, and principal investigator for the compatibility study and leading enrolling investigator in the FLASH study.1 "I have seen firsthand the promise this therapy can offer patients and was happy to build upon our knowledge working with [SGX301] in a clinical setting reflective of real-world use.”

All of the patients in this study had improvements in their cumulative mCAILS score. The average improvement was 36.4% (range, 8%-100%). Looking at individual lesions, results showed that 7 of the 27 index lesions (25.9%) had at least a 50% improvement in their mCAILS score, and 4 of the 27 index lesions (14.8%) were completely resolved after at least 8 weeks of treatment.

Investigators also explored measurements of systemic exposure and electrocardiograms. These findings showed very low and limited levels of systemic hypericin detected in the blood. There was also no impact to normal sinus rhythm observed. Each of these reinforces the safety of treatment with SGX301.

“The ease at which photodynamic therapy with [SGX301] is conducted and the outstanding safety profile we continue to see as demonstrated by the systemic exposure and cardiac results reviewed in this paper makes me very excited for its potential future clinical use. I look forward to participating in the confirmatory phase 3 FLASH2 study later this year," Poligone added.

About SGX301

SGX301 is a novel, first-in-class, photodynamic therapy of topical hypericin. The agent has been shown to be safe as a treatment option for patients with CTCL. However, experts are still unsure about its efficacy, absorption, and effect on heart function parameters in patients who require greater SGX301 exposure, according to the publication in JEADV.

SGX301 has been granted orphan drug and fast track designations from the FDA, as well as orphan designation from the European Medicines Agency. In May 2023, the FDA also granted a type A meeting to discuss the design of a second trial of SGX301 in patients with CTCL following positive results from the phase 3 FLASH study.⁴

A second, confirmatory study titled FLASH2 will soon begin to further evaluate SGX301 in this patient population.¹ The randomized, double-blind, placebo-controlled, multicenter study will enroll about 80 patients with early-stage CTCL, replicating the double-blind, placebo-controlled design used in the phase 3 FLASH study.

FLASH2 will extends the double-blind, placebo-controlled assessment to 18 weeks of continuous treatment. The primary end point assessment will occur at the end of the 18-week timepoint. All important clinical study design components will be the same in this study as they were in the first FLASH study, including the primary end point and key inclusion-exclusion criteria.

REFERENCES:

1. Positive clinical results from HyBryte™ compatibility study in the treatment of cutaneous T-cell lymphoma published in JEADV clinical practice. News release. Soligenix, Inc. May 16, 2024. Accessed May 19, 2024. https://tinyurl.com/y9nstrx9

2. Alexander-Savino CV, Rumage A, Pullion C, et al. Compatibility study of topical 0.25% hypericin (HyBryteTM) application in subjects with mycosis fungoides: Results of the HPN-CTCL-02 study. JEADV Clin Pract. 2024; 1-10. doi:10.1002/jvc2.442

3. Kim EJ, Mangold AR, DiSimone JA, et al. Efficacy and safety of topical hypericin photodynamic therapy for early-stage cutaneous T-cell lymphoma (Mycosis Fungoides). The FLASH phase 3 randomized clinical trial. JAMA Dermatol. 2022;158(9):1031-1039. doi:10.1001/jamadermatol.2022.2749

4. Soligenix announces scheduling of type A meeting with the U.S. FDA to review proposed study design for a second phase 3 study evaluating HyBryte™ in the treatment of cutaneous t-cell lymphoma. News release. Soligenix, Inc. May 11, 2023. Accessed May 19, 2024. https://prn.to/4551VJh