moxetumomab pasudotox
Trade name: Lumoxiti
Approved
Sep 13, 2018
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. This toxin is a 38 kDa fragment of Pseudomonas exotoxin A. — Wikipedia
Clinical trial activity
14 trials · 10 clinical orgs · 2 marketing orgs
Earliest trial started Mar 1, 2007 (NCT00457860)
Timeline
2000s
- Jan 1, 2007
Earliest Phase 1 Sponsor(trial)
- Nov 15, 2007
Orphan Drug Designation
2010s
- Jan 1, 2013
Earliest Phase 3 Sponsor(trial)
- Jan 1, 2014
Earliest Phase 2 Sponsor(trial)
- Sep 13, 2018
AstraZeneca — Earliest FDA Approval
- Sep 13, 2018
AstraZeneca — Marketing Organization
- Sep 13, 2018
AstraZeneca — NDA Organization
- Sep 13, 2018
Innate Pharma — Marketing Organization
- Sep 13, 2018
Innate Pharma — NDA Secondary Org
Indications
Approved for
Studied for
- Leukemia · Phase 1/Phase 2
- Leukemia, Hairy Cell · Phase 3
- Leukemia, Lymphocytic, Chronic, B-Cell · Phase 1/Phase 2
- Leukemia, Lymphoid · Phase 2
- Leukemia, Prolymphocytic · Phase 1
- Lymphoma · Phase 1
- Lymphoma, Non-Hodgkin · Phase 1/Phase 2
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma · Phase 2
- Precursor Cell Lymphoblastic Leukemia-Lymphoma · Phase 1
Mechanism of action
- CD22BINDING AGENT
CD22 binding agent
The Fv at the amino terminus binds to CD22 present on the B-cell malignancy being targeted, and the carboxyl terminal lysine residue at position 613 is rapidly removed by plasma carboxypeptidase, generating a protein ending in REDL. Very soon after binding, the recombinant immunotoxin-CD22 complex is internalized through clathrin-coated pits into the endocytic compartment, where 2 steps occur: (i) reduction of the disulfide bond in domain II, and (ii) a furin-catalyzed cleavage in the middle of
- Elongation factor 2INHIBITOR
Elongation factor 2 inhibitor
The Fv at the amino terminus binds to CD22 present on the B-cell malignancy being targeted, and the carboxyl terminal lysine residue at position 613 is rapidly removed by plasma carboxypeptidase, generating a protein ending in REDL. Very soon after binding, the recombinant immunotoxin-CD22 complex is internalized through clathrin-coated pits into the endocytic compartment, where 2 steps occur: (i) reduction of the disulfide bond in domain II, and (ii) a furin-catalyzed cleavage in the middle of
- CD22ANTAGONIST
CD22 antagonist
The Fv at the amino terminus binds to CD22 present on the B-cell malignancy being targeted, and the carboxyl terminal lysine residue at position 613 is rapidly removed by plasma carboxypeptidase, generating a protein ending in REDL. Very soon after binding, the recombinant immunotoxin-CD22 complex is internalized through clathrin-coated pits into the endocytic compartment, where 2 steps occur: (i) reduction of the disulfide bond in domain II, and (ii) a furin-catalyzed cleavage in the middle of
- CD22INHIBITOR
CD22 inhibitor
- CD22OTHER
CD22 other
The Fv at the amino terminus binds to CD22 present on the B-cell malignancy being targeted, and the carboxyl terminal lysine residue at position 613 is rapidly removed by plasma carboxypeptidase, generating a protein ending in REDL. Very soon after binding, the recombinant immunotoxin-CD22 complex is internalized through clathrin-coated pits into the endocytic compartment, where 2 steps occur: (i) reduction of the disulfide bond in domain II, and (ii) a furin-catalyzed cleavage in the middle of
Approval history
- approvedPriority reviewFast trackSep 13, 2018
Chemistry & pharmacology
- Chirality
- Single Stereoisomer
- Inorganic
- No
- Polymer
- No
- Delivery
- Parenteral
- Multi-specific
- No
- Payload
- Pseudomonas exotoxin A
Oral
No
Parenteral
Yes
Topical
No
Sources
- WikipediaMoxetumomab pasudotox ↗
- NCATS2NDX4B6N8F ↗
- ChEMBLCHEMBL1743043 ↗
Also known as
- cat-8015
- cat-8015
- cat-8015
- ha22
- immunotoxin ha22
- moxetumomab pasudotox
- moxetumomab pasudotox
- moxetumomab pasudotox
- moxetumomab pasudotox
- moxetumomab pasudotox-tdfk
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT03805932 | Phase 1 | Jul 5, 2019 | National Cancer Institute (NCI) |
| NCT02338050 | Phase 2 | May 1, 2015 | Center for International Blood and Marrow Transplant Research, MedImmune, National Institutes of Health (NIH), National Marrow Donor Program, St. Baldrick's Foundation, University of Southern California |
| NCT02227108 | Phase 2 | Aug 1, 2014 | MedImmune |
| NCT01891981 | Phase 1/Phase 2 (Phase 2) | Dec 17, 2013 | MedImmune, University of Texas at Houston |
| NCT01829711 | Phase 3 | Apr 29, 2013 | MedImmune |
| NCT01030536 | Phase 1/Phase 2 (Phase 2) | Mar 1, 2010 | MedImmune |
| NCT00659425 | Phase 1 | Sep 1, 2008 | MedImmune, National Cancer Institute (NCI) |
| NCT00587015 | Phase 1 | Aug 1, 2007 | MedImmune |
| NCT00515892 | Phase 1 | Aug 1, 2007 | Cambridge Antibody Technology |
| NCT00586924 | Phase 1 | May 1, 2007 | Cambridge Antibody Technology, MedImmune |
| NCT00462189 | Phase 1 | Apr 1, 2007 | Cambridge Antibody Technology |
| NCT00587457 | Phase 1 | Mar 1, 2007 | Cambridge Antibody Technology, MedImmune |
| NCT00457860 | Phase 1 | Mar 1, 2007 | Cambridge Antibody Technology |
| NCT03501615 | N/A | — | AstraZeneca, MedImmune |
Organizations
Research & Development (10)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| MedImmune | For profit | 10 | 7 | 4 | 2007 |
| Cambridge Antibody Technology | For profit | 5 | 3 | 1 | 2007 |
| National Cancer Institute (NCI) | Government | 2 | 1 | 1 | 2008 |
| AstraZeneca | For profit | 1 | 1 | 1 | — |
| Center for International Blood and Marrow Transplant Research | Government | 1 | 1 | 1 | 2015 |
| National Institutes of Health (NIH) | Government | 1 | 0 | 1 | 2015 |
| National Marrow Donor Program | Government | 1 | 0 | 1 | 2015 |
| St. Baldrick's Foundation | Academic/Hospital | 1 | 0 | 1 | 2015 |
| University of Southern California | Academic/Hospital | 1 | 0 | 1 | 2015 |
| University of Texas at Houston | Academic/Hospital | 1 | 1 | 1 | 2013 |
Marketing (4)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| AstraZeneca | For profit | MKTG | Sep 13, 2018 |
| AstraZeneca | For profit | NDA | Sep 13, 2018 |
| Innate Pharma | For profit | MKTG | Sep 13, 2018 |
| Innate Pharma | For profit | NDA2 | Sep 13, 2018 |