Efficacy

Efficacy of Rydapt (midostaurin) in Leukemia

Rydapt, known generically as midostaurin, is a targeted therapy approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive, as detected by an FDA-approved test. It is used in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy. The efficacy of Rydapt in this setting was demonstrated in a pivotal phase III clinical trial (the RATIFY trial), which showed a significant improvement in overall survival when Rydapt was added to standard chemotherapy, compared to chemotherapy alone. Patients who received Rydapt had a median overall survival of 74.7 months, compared to 25.6 months for those who received placebo.

Furthermore, Rydapt has also shown efficacy in the treatment of adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL). These are rare forms of leukemia that are associated with the presence of the KIT D816V mutation. Clinical trials have demonstrated that Rydapt can lead to reductions in mast cell burden and improvements in symptoms and quality of life for patients with these conditions.

Efficacy of Asparlas (calaspargase pegol-mknl) in Leukemia

Asparlas, or calaspargase pegol-mknl, is a novel formulation of the enzyme asparaginase, which is used as part of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL). Asparlas has been specifically designed to provide a longer circulating half-life than native asparaginase, allowing for less frequent dosing. The efficacy of Asparlas was established based on the demonstration of achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL, a threshold believed to be necessary for activity against ALL cells. Clinical trials have shown that Asparlas is effective in maintaining this therapeutic threshold with a dosing schedule of once every three weeks.

In a clinical study that supported the approval of Asparlas, patients with ALL received either Asparlas or native E. coli asparaginase as part of a multi-agent chemotherapeutic regimen. The study met its primary endpoint of demonstrating that a high proportion of patients treated with Asparlas maintained the therapeutic level of asparaginase activity. This efficacy, combined with the extended dosing interval, offers a beneficial treatment option for patients with ALL, potentially reducing the treatment burden and improving patient compliance.