FDA Type A Meeting Requested to Discuss SGX301 in Early-Stage CTCL

A type A meeting request has been submitted to the FDA to discuss the contents of a refusal to file (RTF) letter that was previously issued by the FDA regarding the new drug application (NDA) for SGX301 (HyBryte) for patients with early-stage cutaneous T-cell lymphoma (CTCL).¹

SGX301 is a novel, first-in-class, photodynamic therapy and synthetic hypericin that uses safe, visible light for activation and allows for deeper penetration into the skin, avoiding the risk of secondary malignancies.

Previously, SGX301 demonstrated statistically significant results in a phase 3 clinical trial. However, in February 2023, the FDA issued an RTF letter stating that the application was not complete.

Soligenix has now requested a Type A meeting with the FDA to get clarity around the item needed to complete the NDA, and any other next steps. The meeting is expected to occur in approximately 30 days.

"Participating in a Type A meeting with the FDA will be an important next step towards enabling [SGX301’s] advancement through the regulatory process," Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, stated in the press release. "We believe the briefing package submitted with our request addresses the items raised in the RTF letter and will assist with discussions regarding the NDA. We will provide further updates once the meeting has been scheduled with the FDA."

SGX301 has already received orphan drug and fast track designations from the FDA, and an orphan drug designation from the European Medicines Agency (EMA).

The NDA for SGX301 that was submitted to the FDA was supported by findings from the FLASH multicenter, placebo-controlled, double-blind, randomized phase 3 trial (NCT02448381). FLASH was conducted at 39 academic and community centers and included patients aged 18 years and older with stage IA or IIA mycosis fungoides CTCL (MF/CTCL). Treatment with SGX301 was found to be effective and well tolerated in patients with early-stage MF/CTCL.²

In the trial, patients were randomly assigned in a 2:1 fashion to hypericin vs placebo to 3 index lesions twice weekly for 6 weeks during cycle 1 and 6 weeks to index lesions during cycle 2. In cycle 3, which was optional, index and additional lesion were treated for 6 weeks.

The primary end point of the study was to assess index lesion response rate (ILRR) from baseline to week 6 for cycle 1, and the secondary end point of the trial was open-label response rates during cycles 2 and 3. Adverse events (AEs) during each visit and after each cycle, then monthly for a 6-month period were also assessed.

According to results from the 169 patients treated in FLASH, the ILRR was 16% for those treated with topical synthetic hypericin vs 4% for those administered placebo (P = .04).

A 40% increase in TLRR was observed in patients who received 2 cycles of the treatment (P < .001), and significant clinical responses were seen in all of the subgroups of patients included in the study.

Then, in the optional third cycle which focused on safety of patients, 66% of patients continued. In the subset of patients given SGX301 throughout all 3 cycles of treatment, 49% had a positive treatment response (P < .0001) compared with patients receiving placebo in cycle 1.1

In terms of safety, the most common treatment-related AEs seen for patients given the synthetic hypericin vs the placebo group were mild local skin reactions and application-site reaction, and no serious treatment-related AEs were observed.²

REFERENCES:

1. Soligenix submits type A meeting request to U.S. FDA for HyBryte™ new drug application in the treatment of cutaneous T-cell lymphoma. News release. Soligenix, Inc. March 9, 2023. Accessed March 10, 2023. https://bit.ly/3mFMWE0

2. 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