FDA Receives Type A Meeting Request for Synthetic Hypericin in Early-stage Cutaneous T-cell Lymphoma

Article

Soligenix has submitted a Type A meeting request to the FDA to discuss the contents of a refusal to file letter from the regulatory agency regarding the new drug application for synthetic hypericin for the treatment of early-stage cutaneous T-cell lymphoma.

FDA

FDA

Soligenix has submitted a Type A meeting request to the FDA to discuss the contents of a refusal to file letter from the regulatory agency regarding the new drug application (NDA) for synthetic hypericin (HyBryte; SGX301) for the treatment of early-stage cutaneous T-cell lymphoma (CTCL).1

On February 14, 2023, the FDA issued the refusal to file letter after the regulatory agency determined that the NDA was not sufficiently complete to permit substantive review.2

"Participating in a Type A meeting with the FDA will be an important next step towards enabling [hypericin’s] advancement through the regulatory process," Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, stated in a news release.1 "We believe the briefing package submitted with our request addresses the items raised in the refusal to file letter and will assist with discussions regarding the NDA. We will provide further update once the meeting has been scheduled with the FDA."

Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions overtaken by malignant T-cells, and the agent is activated by visible light approximately 24 hours later. Compared with ultraviolent light, visible light on the red/yellow spectrum can penetrate more deeply into the skin, which could allow hypericin to penetrate to treat deeper skin disease and thicker plaques and lesions.

The company filed the NDA based on findings from the phase 3 FLASH trial (NCT02448381), which showed that 16% of patients treated with hypericin (n = 116) experienced a response, defined as a reduction in skin lesions of at least 50%, at week 8 in the first treatment cycle, compared with 4% of patients treated with placebo (n = 50; P = .04).

In the second treatment cycle, patients treated with 12 weeks of hypericin (n = 110) achieved a response rate of 40% (P < .0001 vs placebo treatment rate in cycle 1). Additionally, patients treated with 12 weeks of hypericin also experienced a statistically significant improvement in response in cycle 2 compared with patients given 6 weeks of placebo followed by 6 weeks of hypericin (P < .0001). Furthermore, hypericin elicited responses in 42% of patients with plaque lesions (P < .0001 vs placebo in cycle 1) and in 37% of patients with patch lesions (P = .0009 vs placebo in cycle 1).

During the third optional treatment cycle, all patients could elect to receive hypericin, and 49% of patients who received the agent through all 3 treatment cycles achieved a positive treatment response (P < .0001 vs placebo in cycle 1).

The trial enrolled patients with a clinical diagnosis of stage IA, IB, or IIA CTCL (mycosis fungoides) who had a minimum of 3 evaluable, discrete lesions.3 Key exclusion criteria included sun hypersensitivity, photosensitive dermatoses, unhealed sunburn, topical steroids or other topical treatment within 2 weeks of enrollment, or systemic steroids or other systemic therapies for CTCL within 3 weeks of enrollment.

Each treatment cycle lasted 6 weeks and was followed by a 2-week rest period. In cycle 1, patients were randomly assigned 2:1 to receive 0.25% of hypericin applied twice per week or placebo. The treated area was covered for 12 to 24 hours before being treated with 5 J/cm2 fluorescent light.

The primary end point of the trial was responses at week 8 for hypericin vs placebo. Secondary end points included response rates for patients treated in cycles 2 and 3 vs those given placebo in cycle 1, as well as plaque and lesions response rates.

Regarding safety, the most common treatment-related adverse effects (AEs) included mild local skin reactions (13.5% to 17.3% for hypericin in cycles 1 to 3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2% to 6.9% for hypericin in cycles 1 to 3 vs 4% for placebo in cycle 1). No drug-related serious AEs were reported.4

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. March 9, 2023. Accessed March 13, 2023. https://ir.soligenix.com/2023-03-09
  2. Soligenix receives refusal to file letter from US FDA for HyBryte new drug application in the treatment of cutaneous T-cell lymphoma. Soligenix. News release. February 14, 2023. Accessed February 14, 2023. https://ir.soligenix.com/2023-02-14
  3. 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 March 13, 2023. https://clinicaltrials.gov/ct2/show/NCT02448381
  4. Kim EJ, Mangold AR, DeSimone 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
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