Photodynamic Therapy SGX301 Continues to Impress in Phase 3 CTCL Trial Update

Ellen Kim, MD

Updated data from the pivotal phase 3 FLASH trial showed that SGX301 (synthetic hypericin) continued to demonstrate strong clinical activity in patients with cutaneous T-cell lymphoma (CTCL), according to Soligenix, Inc., the manufacturer of the novel first-in-class photodynamic therapy.¹

The phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study randomized 169 patients with stage Ia, Ib, or IIa CTCL in a 2:1 ratio to either SGX301 or placebo. Of the total enrolled population, 166 were evaluable for efficacy. The study comprised three 8-week treatment cycles. Patients received treatment twice weekly for 6 weeks, and investigators measured response following week 8 of each cycle. In the first double-blind treatment cycle (cycle 1), 50 patients received placebo and 116 were treated with SGX301 (0.25% synthetic hypericin).

The findings for cycle 1 showed that at 8 weeks, 16% of patients in the SGX301 arm achieved at least a 50% reduction in their lesions per the CAILS scoring system, compared to only 4% of patients in the placebo group, representing a statistically significant improvement in treatment response (P = .04).

The update shared by Soligenix was the cycle 2 analysis, which showed a significant increase in response to SGX301 after a subsequent 6 weeks of treatment. At the scheduled week 16 assessment, 40% of patients had achieved a ≥50% reduction in their lesions per the CAILS scoring system, a significant benefit over placebo (P <.0001) and compared to just 1 cycle of treatment (P <.0001).

There were no new safety signals at the cycle 2 assessment, with results showing that SGX301 continue to be well tolerated, as it was in cycle 1.

"As anticipated, the data continues to become more compelling with extended SGX301 treatment," lead FLASH study investigator Ellen Kim, MD, director of the Dermatology Clinic, Perelman Center for Advanced Medicine, stated in a press release.

”This treatment response is comparable to other, less safe, treatment alternatives, showing a statistically significant response at just 6 weeks, which continues to significantly increase with more treatment. The response rate at 12 weeks is similar to other therapies, some of which patients must take for more than a year. In addition to the efficacy demonstrated, SGX301 remains well tolerated with a unique mechanism of action that is not associated with DNA damage like other currently available therapies. I look forward to working with Soligenix to move this important new therapy forward with FDA so that patients may access it as soon as possible,” added Kim.

The majority of enrolled patients decided to continue onto the optional treatment cycle 3, in which all subjects could receive SGX301. The investigators reported that cycle 3 results and additional follow-up data will be reported when the final patients on the trial are finished with their designated visits.

"On behalf of everyone at Soligenix, I would like to again extend my sincere appreciation to the patients, families, investigators, and advisors involved in the pivotal phase 3 FLASH study,” Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, said in the press release. “We are extremely pleased with the study results, which demonstrate successful continued treatment with SGX301 and reinforces its potential to be a valuable and life-changing new therapy for patients suffering from early-stage CTCL, which is an orphan disease and area of unmet medical need."

Overall, the armamentarium for CTCL has expanded in recent years. In August 2018, the FDA approved mogamulizumab-kpkc (Poteligeo) for the treatment of patients with CTCL who have received at least 1 prior systemic therapy. The approval is specifically for patients with mycosis fungoides or Sézary syndrome, 2 subtypes of CTCL.

The FDA based its decision on findings from the phase 3 MAVORIC study. Results from the study presented at the 2017 ASH Annual Meeting showed that mogamulizumab reduced the risk of progression or death by 47% compared with vorinostat (Zolinza) in previously treated patients with CTCL.²

In November 2017, the FDA approved brentuximab vedotin (Adcetris) as a treatment for patients with CTCL who have received prior systemic therapy. The approval is specifically for patients with primary cutaneous anaplastic large cell lymphoma and CD30-expressing mycosis fungoides, which are the most common subtypes of CTCL. The FDA considered data from the phase 3 ALCANZA trial, in which brentuximab vedotin induced responses lasting at least 4 months in 56.3% of patients versus 12.5% in patients receiving physician’s choice of standard therapies (P <.001).³

References

1. Soligenix Announces Positive Phase 3 FLASH Study Demonstrates Increased Efficacy with Continued Treatment in Patients with Cutaneous T-Cell Lymphoma. April 30, 2020. https://prn.to/3bY8UrO. Accessed April 30.
2. Kim YH, MD, Bagot M, Pinter-Brown L et al. Anti-CCR4 monoclonal antibody, mogamulizumab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-Cell lymphoma (CTCL): results from the phase III MAVORIC study. Abstract available ahead of 2017 ASH Annual Meeting; December 9-12, 2017; Atlanta, GA. Abstract 817.
3. Kim YH, Whittaker S, Horwitz SM, et al. Brentuximab vedotin demonstrates significantly superior clinical outcomes in patients with CD30-expressing cutaneous T cell lymphoma versus physician's choice (methotrexate or bexarotene): the phase 3 ALCANZA study. Presented at: 58th Annual ASH Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 182.