The European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to resminostat, a drug developed by 4SC AG, for the treatment of cutaneous T-cell lymphoma (CTCL). This designation provides 4SC with several benefits, including protocol assistance, market exclusivity, and fee reductions within the European Union. This follows a similar designation granted by the U.S. Food and Drug Administration (FDA) in September 2023.
Clinical Trial Data
Data from the RESMAIN study, a randomized, controlled clinical trial involving 201 patients with advanced CTCL across Europe and Japan, demonstrated a statistically significant improvement in progression-free survival (PFS) with resminostat compared to placebo. The study revealed a 38% reduction in the risk of disease progression (median PFS: 8.3 months versus 4.2 months; p=0.015; HR: 0.623 (95%CI: 0.424, 0.916)).
Furthermore, the median time to next treatment was significantly improved with resminostat, showing 8.8 months compared to 4.2 months with placebo (p=0.002; HR: 0.594 (95% CI: 0.424, 0.916)). The side effects of resminostat were reported as mainly mild to moderate, manageable, and reversible.
Additional analyses indicated a clinically meaningful improvement in median "total" PFS (defined from the start of the last prior therapy to disease progression) of 24.3 months in the resminostat group, compared to 14.9 months in the placebo group.
CTCL Treatment Landscape
CTCL is a rare disease characterized by the malignant transformation of T-cells, primarily affecting the skin but potentially involving lymph nodes, blood, and visceral organs. Approximately 5,000 new cases are diagnosed in Europe each year. Current treatment options for advanced-stage CTCL are limited, and while patients may initially respond, the duration of response often diminishes as the disease progresses. The key therapeutic challenge lies in prolonging remissions by halting disease progression and enhancing patients' quality of life.
Resminostat Mechanism and Development
Resminostat is an orally administered inhibitor of class I, IIb, and IV histone deacetylases (HDAC). It has shown promise in inhibiting tumor growth and proliferation, inducing tumor regression, and strengthening the body's immune response to cancer. 4SC is currently investigating resminostat in a pivotal study for CTCL maintenance treatment in Europe, while Yakult Honsha is conducting studies in Japan.
Implications of Orphan Drug Designation
"CTCL is currently an incurable disease and patients are in great need of better therapies," said Jason Loveridge, Ph.D., CEO of 4SC. "Receiving orphan drug designation provides us with a number of important benefits for resminostat (Kinselby), most crucially 10 years’ market exclusivity in the European Union, and, alongside our Orphan Drug Designation in the US, provides us with a solid foundation for our efforts to commercialise Kinselby in these major markets."
