FDA Grants SGX301 a Type A Meeting for the Treatment of CTCL

The FDA has granted a type A meeting to discuss the design of a second trial of SGX301 (HyBryte) in patients with cutaneous T-cell lymphoma (CTCL) following positive results from the phase 3 FLASH study (NCT02448381).¹

The phase 3 FLASH study enrolled 169 patients, 166 of whom were evaluable, with stage IA, IB or IIA CTCL, and included 3 treatment cycles. Treatments were administered twice weekly for the first 6 weeks and treatment response was determined at the end of the 8th week of each cycle.

Throughout the 3 treatment cycles and the 6-month follow-up period, data revealed that SGX301 demonstrated statistically significant results, and the mechanism of action of the product is not associated with DNA damage. This makes SGX301 a safer alternative compared with currently available therapies, all of which are associated with significant and sometimes fatal, adverse events, including the risk of melanoma and other malignancies, risk of significant skin damage, and premature skin aging.

"Responding to FDA feedback, Soligenix has submitted a confirmatory phase 3 draft study protocol retaining the key aspects of the first phase 3 trial," stated Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, in the press release. "We look forward to discussing the protocol in detail with the FDA. We intend to provide a further update once we have received the minutes from the meeting or when we have more clarity on next steps, which we anticipate having by or before the end of June.”

To be included in the trial, patients must have had Stage IA, Stage IB, or Stage IIA clinical diagnosis of CTCL (mycosis fungoides), have a minimum of 3 evaluable, discrete lesion, and have refrained from sunbathing for the duration of the study.²

The first double-blind treatment cycle administered SGX301 to 116 patients (0.25% synthetic hypericin) and placebo to 50.¹ In this cycle, 16% of the patients given SGX301 achieved at least a 50% reduction in their lesions vs 4% of those in the placebo group at 8 weeks (P = .04). In this first cycle, SGX301 was safe and well-tolerated.

In cycle 2, all patients were given SGX301 for the treatment of their index lesions. A total of 110 patients received SGX301 for 12 weeks and 45 received 6 weeks of placebo followed by 6 weeks of SGX301 treatment. Among the 12-week treatment group, the response rate was 40% (P < .0001 vs the placebo treatment rate in cycle 1). Through comparing the 12-week and 6-week treatment groups, a statistically significant improvement (P <.0001) was seen, showing that continued treatment results in better outcomes.In this arm, SGX301 continued to be safe and well-tolerated.

According to additional analyses, SGX301 was equally effective in treating both plaque (response 42%, P <.0001 relative to placebo treatment in cycle 1) and patch (response 37%, P = .0009 relative to placebo treatment in cycle 1) lesions of CTCL.

Lastly, cycle 3 was focused on safety and all patients had the option to receive SGX301 for the treatment of all their lesions. A total of 66% of patients chose to continue with this optional cycle of the study, and 49% demonstrated a positive treatment response (P <.0001 compared with patients receiving placebo in cycle 1). This cycle also demonstrated that SGX301 is not systemically available, consistent with the general safety of this topical product observed to date, and despite extended and increased use of the product to treat multiple lesions, SGX301 remained well-tolerated.

Overall, these findings show that SGX301 potentially represents the safest available efficacious treatment for patients with CTCL.

To further assess SGX301, investigators evaluated the product in a compatibility study for the treatment of CTCL using the commercially ready Daavlin Series 7 visible light device.³ In the open-label study, 9 patients were enrolled and received SGX301 for 8 weeks for their cancerous lesions, with an assessment of treatment response that was conducted at week 10 using the Composite Assessment of Index Lesion Severity (CAILS) score.

The goal of the trial was to establish that any light device capable of producing visible light of an appropriate and consistent wavelength (500 to 650 nm) was suitable for use with SGX301, as well as to extend the pharmacokinetic profile using a recently developed, more sensitive hypericin assay.

While patients in this study were selected to have more extensive disease consistent with its potential commercial use, finding showed that the treatment response was 22% following 8 weeks of twice weekly SGX301 therapy, summarizing the results of the FLASH trial. All patients had improvements in their cumulative CAILS score with an average improvement of 36.4% (range, 8%-100%). Looking at individual lesions, 7 of the 27 index lesions (25.9%) had at least a 50% improvement in their CAILS score and 4 of the 27 index lesions (14.8%) resolved completely after a minimum of 8 weeks of treatment. Measurements of systemic exposure and cardiac output showed low and limited levels of systemic hypericin detected in the blood, and there was no observable impact to normal sinus rhythm. These findings reinforce the safety of SGX301.

"These results reinforce the positive [SGX301] data from the FLASH study. Important corporate objectives for the study were to replicate results previously observed in the FLASH study, while using finished drug products manufactured by our proposed commercial contract manufacturer and activated using a commercially viable light device," added Schaber, in a press release. "We look forward to continuing to work with [Brian Poligone, MD, PhD] and all of our committed clinical investigators to make [SGX301] available to this underserved orphan patient population."

REFERENCES:

1. 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 15, 2023. https://prn.to/4551VJh

2. FLASH [fluorescent light activated synthetic hypericin] clinical study: topical SGX301 (synthetic hypericin) for the treatment of cutaneous T-cell lymphoma (mycosis fungoides). ClinicalTrials.gov. Updated April 15, 2022. Accessed May 15, 2023. https://clinicaltrials.gov/ct2/show/NCT02448381

3. Soligenix announces positive clinical results from compatibility study of HyBryte™ in the treatment of cutaneous T-cell lymphoma. News release. Soligenix, Inc. May 4, 2023. Accessed May 15, 2023. https://bit.ly/3MscA9G