0% versus 20%) for patients 65 years of age orolder as compared to those younger than 65 years.
Clinical studies of LUMOXITI did not includesufficient numbers of subjects aged 65 and over to determine whether there were differences in efficacybetween younger and older patients.
11 DESCRIPTION
Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin. Moxetumomab pasudotox-tdfk is composedof a recombinant, murine immunoglobulin variable domain genetically fused to a truncated form ofPseudomonas exotoxin, PE38, that inhibits protein synthesis. Moxetumomab pasudotox-tdfk has anapproximate molecular weight of 63 kDa and is produced in E. coli cells by recombinant DNAtechnology. During the moxetumomab pasudotox-tdfk manufacturing process, fermentation is carried outin nutrient medium containing the antibiotic kanamycin. However, kanamycin is cleared in themanufacturing process and is not detectable in the final product.
LUMOXITI (moxetumomab pasudotox-tdfk) for injection is supplied as a sterile, preservative-free, whiteto off-white lyophilized cake or powder in a single-dose vial for reconstitution and dilution prior tointravenous infusion. Each single-dose vial contains 1 mg moxetumomab pasudotox-tdfk, glycine (80mg), polysorbate 80 (0.2 mg), sodium phosphate monobasic monohydrate (3.4 mg), sucrose (40 mg), andsodium hydroxide to adjust pH to 7.4. After reconstitution with 1.1 mL Sterile Water for Injection, USP,the resulting 1 mg/mL solution allows a withdrawal volume of 1 mL. Prior to intravenous infusion, thereconstituted vial(s) of solution are added to an infusion bag containing 50 mL of 0.9% Sodium ChlorideInjection, USP and 1 mL of IV Solution Stabilizer.
IV Solution Stabilizer is a sterile, preservative-free, colorless to slightly yellow, clear solution free fromvisible particles and supplied in a single-dose vial. Each vial contains 1 mL solution. Each vial containscitric acid monohydrate (0.7 mg), polysorbate 80 (6.5 mg), sodium citrate dihydrate (6.4 mg), and Waterfor Injection, USP. The pH is 6.0.
The LUMOXITI and IV Solution Stabilizer vial stoppers are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin. Moxetumomab pasudotox-tdfk binds CD22on the cell surface of B-cells and is internalized. Moxetumomab pasudotox-tdfk internalization results inADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death.
12.2 Pharmacodynamics The presence of moxetumomab pasudotox-tdfk may interfere with detection of cellular CD22, therefore,total peripheral blood B-cell counts (including normal B cells and HCL cells) were quantified using astandard assay for CD19+ B cells as a surrogate. In patients with HCL, treatment with LUMOXITI at theapproved recommended dosage resulted in a reduction of circulating CD19+ B cells.
The circulatingCD19+ B cells on Day 8 were reduced by 89% from baseline following the first three infusions ofLUMOXITI. B cell reduction was sustained for at least 1-month post-treatment.
Total counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+/CD56 Natural Killer cells andquantitative immunoglobulin (Ig) A, G, and M levels were eva luated throughout the course of treatment.
On Day 8, median cell counts were reduced from baseline for the following populations: CD3+ T cells(-21%), CD4+ T cells (-20%), CD8+ T cells (-23%), and CD16+/CD56 Natural K |
