Post-treatment data from the HPN-CTCL-04 study comparing HyBryte (synthetic hypericin) to Valchlor (mechlorethamine) demonstrated continued improvement in HyBryte treated patients

The study, which enrolled 10 patients randomized 1:1 with 12 weeks of treatment and 4 weeks of follow-up post-treatment, was previously reported to demonstrate a positive difference in the overall per patient treatment response rate (60% in the HyBryte  group vs. 20% in the Valchlor group) at the end of treatment. After the 4-week follow-up period (Week 16), the majority (3 of 5) of HyBryte patients continued to demonstrate improvement with at least a further 10% improvement (absolute difference) at Week 16 relative to the primary outcome measure at Week 12, including one of the HyBryte™ patients achieving a "complete response".

 In contrast, of the four patients that completed the Valchlor arm of the study, none achieved this level of improvement by Week 16. For patients, a treatment response was defined as a ≥50% improvement in their cumulative mCAILS (modified Composite Assessment of Index Lesion Severity) score over 3 to 5 lesions. Treatment response was also assessed on individual lesions. There was a similar continued improvement in the lesion responses over time, with the plaque lesions of particular interest given their increasing association with risk of overall disease progression and long-term mortality. At the 12-week (end of treatment) timepoint, the HyBryte treated plaque lesions were statistically significantly improved compared to the Valchlor treated plaques (63%, [10/16] treatment success with HyBryte vs. 17%, [2/12] with Valchlor, p=0.02). By Week 16, the response rates in lesions treated with HyBryte were statistically significant responses for all lesions (72% HyBryte vs 28% Valchlor, p=0.02) and specifically for plaque lesions (75% responding plaque lesions with HyBryte treatment vs. 17% with Valchlor, p=0.006) relative to the Valchlor group. No safety concerns with HyBryte were raised during the follow-up period.

"Following the positive results from the previous Phase II and III studies where we previously participated in evaluating HyBryte, we were excited to support Soligenix's effort to conduct a prospective comparative assessment of HyBryte versus Valchlor," stated Dr. Brian Poligone, Director of the Rochester Skin Lymphoma Medical Group, and Principal Investigator for the comparability study. "Despite the small study sample size and a randomization that resulted in the HyBryte group having patients with more extensive disease, HyBryte continues to demonstrate its rapid onset of action and benign safety profile, compared to one of the most widely prescribed approved drugs for early-stage CTCL. The potentially enhanced effect on plaque lesions mirrors the promising activity against very difficult to treat lesions, such as refractory folliculotropic lesions, which we also observed in the first Phase 3 study. We look forward to continuing our support of Soligenix in the development of HyBryte by participating in the upcoming confirmatory Phase III placebo-controlled study."

"These results support the positive HyBryte data from the previously completed Phase III FLASH study and demonstrates that a relatively short treatment period with the drug can result in clinically meaningful outcomes," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "This relatively rapid response to HyBryte therapy fits nicely into the treatment arsenal for CTCL and reinforces the relative safety of HyBryte in these patients compared to other therapies currently in use. We look forward to continuing to work with Dr. Poligone and all of our committed clinical investigators to initiate the 80-patient confirmatory Phase III replication study (FLASH2) next month."

The purpose of the HPN-CTCL-04 study was to obtain preliminary comparative assessment of the safety and efficacy of Valchlor versus HyBryte following 12 weeks of treatment as measured in 3 to 5 prospectively identified index lesions for each patient. HyBryte  was administered twice weekly with light exposure approximately 24 hours after drug application, while Valchlor was applied as often as daily as per the package insert. At the end of the 12-week treatment period, 60% of the HyBryte patients met the prospectively defined level of "Treatment Success" (≥50% improvement in their cumulative mCAILS score compared to Baseline) compared to only 20% of the Valchlor patients; although due to the small sample size the results do not achieve statistical significance. Of the remaining two HyBryte patients that did not achieve treatment success, both saw a substantial (≥30%) reduction in their mCAILS score. In contrast, in the Valchlor group, of the remaining 4 patients that did not achieve treatment success, one worsened and dropped from the study, one improved less than 30% and two improved ≥30%. The average cumulative improvement in mCAILS at 12 weeks was 52.5% in the HyBryte patients versus 34.7% in the Valchlor patients. HyBryte was well tolerated in all patients whereas 1 of the 5 patients receiving Valchlor had to be withdrawn from the trial because of a clinically significant allergic contact dermatitis from Valchlor.

During the 4-week follow-up period (Week 16) the majority (3 of 5) of HyBryte patients continued to demonstrate lesion improvement with at least a further 10% reduction (absolute difference) at Week 16 relative to the primary outcome measure at Week 12, including one of these patients achieving a "complete response". The remaining two HyBryte  subjects showed either a modest (<5%) decrease or increase relative to their primary endpoint response at Week 12. In contrast, of the four patients that completed the Valchlor arm of the study, one worsened (>15% change), one had a modest decrease, one remained static, and one had a modest improvement by Week 16. Analysis of the individual lesion responses showed similar response profiles, with treatment response observed in 61% of HyBryte treated lesions vs. 33% response in Valchlor treated lesions (p=0.18) at Week 12. The lesions responses increased over the 4 weeks following treatment to 72% responding lesions with HyBryte treatment and decreased over the 4 weeks following treatment to 28% with Valchlor, p=0.02. Focusing specifically on the plaque lesions, 63% of HyBryte treated plaque lesions (10/16) responded to treatment vs. 17% of Valchlor treated plaque lesions (2/12; p=0.02). Again, the responses of the HyBryte treated lesions increased over the 4 weeks following treatment to 75% responding plaque lesions with HyBryte treatment and the Valchlor treated lesions response rate was unchanged at 17%, p=0.006. Plaque lesions have been acknowledged as both more difficult to treat and, more recently, as potentially linked to disease progression. The link with disease progression was most recently reported at the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Tumour Group Annual Meeting in Lausanne, Switzerland on October 9-11, 2024.

When comparing the tolerance of the topical therapies (i.e., reactions where the drug was applied to the skin) in this trial, it is notable that all patients tolerated HyBryte well and had no adverse events "Related" to the therapy. In contrast, 60% of the Valchlor treated patients had at least one adverse event "Related" to the therapy. These adverse events in the Valchlor group included rashes, application site sensitivity, allergic contact dermatitis, and dermatitis, with one patient requiring steroid treatment, one requiring temporary interruption of Valchlor treatments, and one requiring permanent discontinuation of Valchlor. No such instances were reported in the HyBryte group.