The FDA has granted orphan drug designation to tigilanol tiglate (Stelfonta), marking a significant regulatory milestone for QBiotics Group Limited's novel intratumoral injection in the treatment of soft tissue sarcoma. The designation recognizes the agent's potential as a new therapeutic option for this rare and life-threatening disease.
"The prognosis of advanced soft tissue sarcoma patients remains unfavorable and new treatments are urgently needed," said Victoria Gordon, PhD, executive director of Strategic Alliances and Investor Relations at QBiotics. "The FDA Orphan Drug Designation for tigilanol tiglate signals an important milestone for QBiotics, reflecting its recognition by the FDA as a potential new treatment option for this debilitating and life-threatening disease."
Regulatory Benefits and Market Impact
Orphan drug designation qualifies sponsors for several important incentives, including tax credits, user fee exemption, and a potential seven years of market exclusivity following approval. This regulatory pathway is specifically designed for agents that prevent, diagnose, or treat rare diseases.
The designation comes as soft tissue sarcomas represent a significant unmet medical need. These rare tumors constitute more than 80 subtypes affecting both adults and children. In 2021, 124,573 new cases of soft tissue sarcoma were reported globally, with an annual incidence growth rate of 0.54%. Approximately 13,590 new cases are projected for 2024.
Current Clinical Development
Tigilanol tiglate is currently being evaluated in the phase 2a QB46C-H07 trial (NCT05755113) at Memorial Sloan Kettering Cancer Center in New York. The open-label, single-arm study aims to enroll approximately 10 adult patients with soft tissue sarcomas of the extremities and body wall.
The study's primary endpoint is tumor response, while secondary endpoints include incidence of adverse events and systemic exposure. Investigators are also evaluating the tumor microenvironment, peripheral blood mononuclear cells, and local recurrence rate at injection sites.
Eligible patients receive single or multiple injections of tigilanol tiglate at up to a fixed dose of 3.6 mg/m2. Patients with unresectable tumors may receive treatment at 28-day intervals for up to five treatments, while those eligible for surgery receive a single intratumoral treatment with surgery scheduled 28 days post-injection.
Promising Phase 1 Results
Previous phase 1 data from an Australian study demonstrated encouraging efficacy signals. The study enrolled 22 patients with accessible cutaneous, subcutaneous, or nodal tumors refractory to conventional therapy. Patients received tigilanol tiglate at dose levels ranging from 0.06 mg/m2 to 3.6 mg/m2.
Efficacy findings showed that 6 of 22 patients demonstrated a response per RECIST 1.1 criteria. One patient treated at the 2.40 mg/m2 dose level achieved a complete response, while three patients experienced partial responses at various dose levels. Ten patients had stable disease, and three patients in a local effect cohort achieved complete responses.
Safety Profile
The safety profile from the phase 1 study showed that most adverse effects were mild to moderate, with 96% of events falling into these categories. Adverse events were reported at grade 1 (n=135), grade 2 (n=81), grade 3 (n=6), and grade 4 (n=2) severities. There was one dose-limiting toxicity, two serious adverse events, and no deaths. The maximum tolerated dose was not reached, but dose escalation stopped at 3.6 mg/m2, which investigators determined provided an appropriate balance between safety and potential efficacy.
Previous FDA Approval
Tigilanol tiglate has regulatory precedent, having received FDA approval in 2020 as a treatment for mast cell tumors in dogs, demonstrating the agency's familiarity with the compound's mechanism and safety profile.
The current phase 2 trial is estimated to be completed in March 2025, with enrollment currently ongoing. As of November 2023, one patient with regionally recurrent myxofibrosarcoma had been treated with tigilanol tiglate, with another patient in screening at that time.
