Moxetumomab pasudotox

Moxetumomab pasudotox, sold under the brand name Lumoxiti, is an anti-CD22 immunotoxin medication for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Moxetumomab pasudotox is a CD22-directed cytotoxin and is the first of this type of treatment for adults with HCL. The drug consists of the binding fragment (Fv) of an anti-CD22 antibody fused to a toxin called PE38.[2] This toxin is a 38 kDa fragment of Pseudomonas exotoxin A.

Hairy cell leukemia (HCL) is a rare, slow-growing cancer of the blood in which the bone marrow makes too many B cells (lymphocytes), a type of white blood cell that fights infection. HCL is named after these extra B cells which look “hairy” when viewed under a microscope. As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells and platelets are produced.

Medical uses

Moxetumomab pasudotox as monotherapy is indicated for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) after receiving at least two prior systemic therapies, including treatment with a purine nucleoside analogue (PNA).

Adverse effects

Common side effects include infusion-related reactions, swelling caused by excess fluid in body tissue (edema), nausea, fatigue, headache, fever (pyrexia), constipation, anemia and diarrhea.

History

On 5 December 2008, orphan designation (EU/3/08/592) was granted by the European Commission to Medimmune Limited, United Kingdom, for murine anti-CD22 antibody variable region fused to truncated Pseudomonas exotoxin 38 for the treatment of hairy cell leukaemia.[13] It was renamed to Moxetumomab pasudotox.[13] The sponsorship was transferred to AstraZeneca AB, Sweden, in January 2019.[13]

On 17 July 2013, orphan designation (EU/3/13/1150) was granted by the European Commission to MedImmune Ltd, United Kingdom, for moxetumomab pasudotox for the treatment of B-lymphoblastic leukaemia / lymphoma.[14] The sponsorship was transferred to AstraZeneca AB, Sweden, in January 2019.[14]

Moxetumomab pasudotox was approved for use in the United States in September 2018.[15]

The efficacy of moxetumomab pasudotox was studied in a single-arm, open-label clinical trial of 80 subjects who had received prior treatment for hairy cell leukemia with at least two systemic therapies, including a purine nucleoside analog.[15] The trial measured durable complete response (CR), defined as maintenance of hematologic remission for more than 180 days after achievement of CR.[15] Thirty percent of subjects in the trial achieved durable CR, and the overall response rate (number of subjects with partial or complete response to therapy) was 75 percent.[15]

The US Food and Drug Administration (FDA) granted the application for moxetumomab pasudotox fast track, priority review, and orphan drug designations.[15][16] The FDA granted the approval of a Biologics License Application for Lumoxiti to AstraZeneca Pharmaceuticals.[15] This was subsequently transferred to Innate Pharma in March 2020.[17]

On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Lumoxiti, intended for the treatment of relapsed or refractory hairy cell leukemia after two prior systemic therapies including a purine nucleoside analog. The orphan designation for Lumoxiti for treatment of hairy cell leukaemia was also maintained.[18] The applicant for this medicinal product is AstraZeneca AB. Moxetumomab pasudotox was approved for medical use in the European Union in February 2021.[19] The EU marketing authorization was withdrawn in July 2021.[19]

verifiedfields	changed
watchedfields	changed
verifiedrevid	458284291
type	mab
mab type	mab
source	o
target	CD22
tradename	Lumoxiti
medlineplus	a618052
dailymedid	Moxetumomab pasudotox
pregnancy category	Contraindicated‡R1R‡
routes of administration	Intravenous
atc prefix	L01
atc suffix	FB02
legal us	Rx-only
legal eu	Rx-only
cas number	1020748-57-5
drugbank	DB12688
chemspiderid	none
unii	2NDX4B6N8F
kegg	D09932
synonyms	moxetumomab pasudotox-tdfk, CAT-8015
c	2804
h	4339
n	783
o	870
s	14

Moxetumomab pasudotox

Medical uses

Adverse effects

Discovery and ownership background

History

External links

References