Moxetumomab Pasudotox

Moxetumomab Pasudotox Uses, Dosage, Side Effects, Food Interaction and all others data.

CD22 is a lineage-restricted B-cell antigen that is expressed solely in on B-chronic lymphocytic leukemia, hairy cell leukemia, acute lymphocytic leukemiathe and Burkitt's lymphoma. The predecessor of Moxetumab pasudotox (MxP), named BL22, was first created based on the antibody RFB4 which specifically binds to CD22. This antibody was used to generate a recombinant immunotoxin in which a stabilized Fv segment by a disulfide bond is fused to the Pseudomonas exotoxin A (PE38) which does not have the cell-binding portion.

MxP appears as an improved form of BL22 by the mutation of the Fv region and the antibody phage-displayed. As well the residues SSY in the heavy chain are mutated to THW. It was developed by Astra Zeneca and FDA approved on September 13, 2018, after being granted the status of Fast Track, Priority Review and Orphan Drug designations.

Compared with its predecessor, MxP is even 50-fold more active on lymphoma cell lines and leukemic cells. In phase I clinical trial, MxP showed no dose-limiting toxicity and the overall response rate was of 79%. From pediatric patients with acute lymphoblastic leukemia, the complete response was observed in 12 individuals which is a result that has never been seen before.

Moxetumomab Pasudotox
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Moxetumomab Pasudotox
Generic	Moxetumomab pasudotox
Moxetumomab pasudotox Other Names	Moxetumomab pasudotox, moxetumomab pasudotox-tdfk
Weight	1mg
Type	Intravenous powder for injection
Formula	C₂₈₀₄H₄₃₃₉N₇₈₃O₈₇₀S₁₄
Weight	63500.0 Da
Protein binding	The main mechanism of action of MxP is done in the plasma and its cells. Thus, this property is not relevant for this drug.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Moxetumomab Pasudotox is a CD22-specific antibody conjugated to a truncated exotoxin used to treat relapsed or refractory hairy cell leukemia in patients who have already been treated with a purine nucleoside analog and one other treatment.

MxP is indicated for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who received at least two prior systemic therapies including treatment with a purine nucleoside analog. The use of this drug is not recommended in patients with severe renal impairment (CrCl < 29 ml/min).

HCL is an uncommon type of lymphocytic leukemia that starts in B cells or B lymphocytes. It is characterized by an accumulation of abnormal B lymphocytes. HCL is called "hairy" as it produces hair-like projections in the surface of the cancer cells. A usual symptom in people having HCL is the presence of splenomegaly and less often hepatomegaly.

Moxetumomab Pasudotox is also used to associated treatment for these conditions: Relapsed/Refractory Hairy Cell Leukemia

How Moxetumomab Pasudotox works

MxP is a CD22-directed cytotoxin. It is stated as an immunotoxin which is defined as the class of agents that combine the selectivity of antibodies towards the target and the potency of toxins to perform the pharmacological anticancer function. CD22 is a B-lymphocyte restricted transmembrane protein with a high density in HCL cells when compared with normal B cells. After binding to CD22, MxP is internalized and processed, which allows the release of the modified toxin. This toxin inhibits protein translation which induces an apoptotic state of the high CD22-expressed cancer cell.

The toxin included in MxP is the Pseudomonas exotoxin A which, after internalization, undergoes conformational changes and in the cytosol, the ribosylation activity of the domain III of the toxin inactivates the eukaryotic translation elongation factor (eEF-2) by transferring ADP (adenosine di-phosphate-ribose) from NAD to a modified histidine at position 715 in eEF-2. This action produces the inactivation of eEF-2 which leads to protein synthesis inhibition and programmed cell death.

Toxicity

No studies have been performed regarding the carcinogenic potential and/or effect on fertility of MxP. It has been observed that the administration of MxP in a dose > 3 times the recommended can produce the degeneration of heart tissue and a dose > 10 times the recommended there are reports of gliosis, axonal degeneration in the spinal cord and body tremors.

Food Interaction

No interactions found.

Volume of Distribution

The mean volume of distribution calculated based on population is 6.5 L.

Elimination Route

MxP serum concentration increases in a dose-proportional manner and reaches a mean steady state of 379 ng/ml with a Cmax of 626 ng.h/ml. There are no reports of systemic accumulation.