The FDA has requested positive results from a second clinical study of SGX301 in patients with early stage cutaneous T-cell lymphoma before filing a new drug application.
During a type a meeting between Soligenix, Inc., and the FDA, the contents of a refusal to file letter previously issued by the FDA regarding the new drug application (NDA) for SGX301 (HyBryte) for use in patients with early-stage cutaneous T-cell lymphoma (CTCL) were discussed.1
In a phase 3 FLASH clinical trial (Study HPN-CTCL-01; NCT02448381), SGX301 demonstrated statistically significant results in this patient population. However, the FDA is requesting positive results from a second clinical study in addition to the phase 3 FLASH study before accepting an NDA filing for SGX301. The FDA is open to engaging in protocol discussions regarding the second clinical study.
Based on the feedback, Soligenix will engage in discussions with the FDA to define the protocol and evaluate the feasibility of conducting an additional clinical trial.
"The phase 3 FLASH study was the largest double-blind, randomized, placebo-controlled clinical trial ever conducted in the CTCL population. While we are surprised that the FDA did not accept our submitted NDA for filing and review, it was very clear that the FDA's thinking has evolved in evaluating CTCL therapies since our initial protocol discussions on Study HPN-CTCL-01 and that another phase 3 study will be required to support an NDA for [SGX301]. During the Type A meeting, we discussed elements of protocol design for the additional confirmatory study and look forward to collaborating with the FDA to advance these discussions as quickly as possible to have a reasonable study design to meet the FDA's requirements," said Christopher J. Schaber, PhD, president, and chief executive officer of Soligenix, in a press release.
SGX301is a novel, first-in-class, photodynamic therapy which uses safe, visible light for activation. This treatment approach also helps avoid the risk of secondary malignancies seen with the frequently employed DNA-damaging drugs that are dependent on ultraviolet exposure.
In a published phase 2 clinical study among patients with CTCL, patients treated with SGX301 had a statistically significant improvement with topical hypericin treatment (P = .04) compared with placebo, as it was ineffective. Previously, SGX301 was granted an orphan drug and fast track designation from the FDA, as well as orphan designation from the European Medicines Agency.
Then, the phase 3 FLASH study enrolled 169 patients, including 166 who were evaluable, with Stage IA, IB or IIA CTCL. Three treatment cycles were utilized in the trial and 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. The FLASH trial 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).2
Those enrolled were randomly assigned in a 2:1 fashion to receive 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 lesions were treated for 6 weeks.
Investigators assessed the primary end point of index lesion response rate (ILRR) from baseline to week 6 for cycle 1, and the secondary end point of 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.
Patients in the first double-blind treatment cycle (n = 116) were treated with SGX301 (0.25% synthetic hypericin) or placebo (n = 50). Among patients receiving SGX301, 16% achieved at least a 50% reduction in their lesions compared with 4% of patients in the placebo group at 8 weeks (P = .04) during the first treatment cycle. In the first cycle, findings demonstrated that SGX301 was safe and well-tolerated.1
In cycle 2, all patients were given treatment with SGX301of their index lesions. Of the 155 patients in this cycle, 110 received 12 weeks of SGX301 treatment and 45 received 6 weeks of placebo treatment followed by 6 weeks of SGX301 treatment. Data showed that the response rate among the 12-week treatment group was 40% (P < .0001 vs the placebo treatment rate in Cycle 1. When comparing the 12-week and 6-week treatment groups, there was also a statistically significant improvement (P < .0001) between the two groups, indicating better outcomes with continued treatment. This second treatment cycle continued to demonstrate the safety and tolerability of SGX301.
The third treatment cycle was optional and focused on safety. All patients enrolled in the first 2 cycles could elect to receive SGX301 of all their lesions, and 66% of patients elected to continue with this cycle of the study. Of the patients that received SGX301 throughout all 3 cycles of treatment, 49% had a positive treatment response compared with patients receiving placebo in cycle 1 (P < .0001).
Additionally, within a subset of patients evaluated in this cycle, SGX301 was not systemically available, which is consistent with the general safety of what is already known with the product. At the end of cycle 3, SGX301 continued to be well-tolerated, even with the extended and increased use of the product to treat multiple lesions.
Each of the 3 treatment cycles demonstrated the overall safety of SGX301. The mechanism of action of SGX301 is not associated with DNA damage. This makes the product a safer alternative than currently available therapies. Overall, treatment with SGX301 represents a potential, safe, and efficacious treatment option for patients with CTCL.
"While we are very disappointed by this delay, Soligenix and its clinical investigators remain committed to working with the FDA and advancing SGX301 to market for patients suffering with CTCL," added Schaber.