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{{Short description|Pharmaceutical drug}} |
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{{Drugbox |
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{{Use dmy dates|date=April 2020}} |
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{{Infobox drug |
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| verifiedrevid = 449168600 |
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| verifiedrevid = 458284291 |
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| type = mab |
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| type = mab |
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| image = |
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| image = |
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| alt = |
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| width = |
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| alt = |
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| caption = |
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<!-- Monoclonal antibody data --> |
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| mab_type = mab |
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| mab_type = mab |
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| source = o |
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| source = o |
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| target = ] |
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| target = ] |
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| tradename = |
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<!-- Clinical data --> |
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| Drugs.com = |
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| MedlinePlus = |
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| pronounce = |
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| tradename = Lumoxiti |
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| Drugs.com = {{drugs.com|monograph|moxetumomab-pasudotox-tdfk}} |
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| MedlinePlus = a618052 |
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| DailyMedID = Moxetumomab pasudotox |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU_comment = |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category= Contraindicated<ref name="Drugs.com pregnancy">{{cite web | title=Moxetumomab pasudotox (Lumoxiti) Use During Pregnancy | website=Drugs.com | date=22 October 2018 | url=https://www.drugs.com/pregnancy/moxetumomab-pasudotox.html | access-date=20 April 2020}}</ref> |
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| pregnancy_category= |
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| routes_of_administration = ] |
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| class = |
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| ATC_prefix = L01 |
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| ATC_suffix = FB02 |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_AU_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F--> |
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| legal_BR_comment = |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_status = |
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| legal_CA_comment = |
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| routes_of_administration = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled--> |
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| bioavailability = |
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| legal_DE_comment = |
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| protein_bound = |
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| metabolism = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| elimination_half-life = |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> |
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| excretion = |
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| legal_UK_comment = |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| legal_US = Rx-only |
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| CAS_number = <!-- blanked - oldvalue: 1020748-57-5 --> |
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| legal_US_comment = <ref name="Lumoxiti FDA label" /> |
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| ATC_prefix = none |
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| legal_EU = Rx-only |
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| ATC_suffix = |
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| legal_EU_comment = <ref name="Lumoxiti EPAR" /> |
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| PubChem = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| legal_UN_comment = |
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| DrugBank = |
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| legal_status = <!-- For countries not listed above --> |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = NA |
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<!-- Pharmacokinetic data --> |
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| C=2804 | H=4339 | N=783 | O=870 | S=14 |
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| bioavailability = |
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| molecular_weight = 63.5 kDa |
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| protein_bound = |
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| metabolism = |
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| metabolites = |
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| onset = |
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| elimination_half-life = |
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| duration_of_action = |
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| excretion = |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = 1020748-57-5 |
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| CAS_supplemental = |
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| PubChem = |
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| IUPHAR_ligand = |
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| DrugBank_Ref = |
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| DrugBank = DB12688 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = none |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = 2NDX4B6N8F |
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| KEGG_Ref = |
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| KEGG = D09932 |
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| ChEBI_Ref = |
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| ChEBI = |
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| ChEMBL_Ref = |
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| ChEMBL = |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = moxetumomab pasudotox-tdfk, CAT-8015 |
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<!-- Chemical and physical data --> |
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| IUPAC_name = |
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| C=2804 | H=4339 | N=783 | O=870 | S=14 |
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| SMILES = |
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| StdInChI = |
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| StdInChI_comment = |
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| StdInChIKey = |
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| density = |
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| density_notes = |
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| melting_point = |
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| melting_high = |
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| melting_notes = |
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| boiling_point = |
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| solubility = |
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| specific_rotation = |
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}} |
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}} |
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'''Moxetumomab pasudotox''', sold under the brand name '''Lumoxiti''', is an anti-] ] medication for the treatment of adults with relapsed or refractory ] (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog.<ref name="Lumoxiti FDA label" /><ref name="Lumoxiti EPAR" /><ref name="FDA PR" /> Moxetumomab pasudotox is a CD22-directed cytotoxin and is the first of this type of treatment for adults with HCL.<ref name="FDA PR" /> The drug consists of the binding fragment (Fv) of an anti-CD22 antibody fused to a toxin called PE38.<ref name="Kreitman et al.">{{cite journal | vauthors = Kreitman RJ, Pastan I | title = Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox | journal = Clinical Cancer Research | volume = 17 | issue = 20 | pages = 6398–405 | date = October 2011 | pmid = 22003067 | pmc = 3201735 | doi = 10.1158/1078-0432.CCR-11-0487 }}</ref> This toxin is a 38 kDa fragment of ] A. |
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'''Moxetumomab pasudotox''' is a mouse monoclonal antibody designed for the treatment of cancer.<ref>{{cite web|title=Statement On A Nonproprietary Name Adopted By The USAN Council: Moxetumomab Pasudotox|publisher=]|url=http://www.ama-assn.org/resources/doc/usan/moxetumomab-pasudotox.pdf}}</ref> |
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Hairy cell leukemia (HCL) is a rare, slow-growing cancer of the blood in which the bone marrow makes too many ] (lymphocytes), a type of white blood cell that fights infection.<ref name="FDA PR" /> HCL is named after these extra B cells which look “hairy” when viewed under a microscope.<ref name="FDA PR" /> As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells and platelets are produced.<ref name="FDA PR" /> |
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Moxetumomab pasudotox was developed by ], Inc. |
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== References == |
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== Medical uses == |
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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).<ref name="Lumoxiti FDA label" /><ref name="Lumoxiti EPAR" /> |
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== Adverse effects == |
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<references/> |
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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.<ref name="Lumoxiti FDA label" /><ref name="Lumoxiti EPAR" /><ref name="FDA PR" /> |
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The prescribing information for moxetumomab pasudotox includes a boxed warning about the risk of developing ], a condition in which fluid and proteins leak out of tiny blood vessels into surrounding tissues.<ref name="Lumoxiti FDA label">{{cite web | title=Lumoxiti- moxetumomab pasudotox injection, powder, lyophilized, for solution IV solution stabilizer solution | website=DailyMed | date=25 January 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6510282-1a57-4614-9859-299a227a089c | access-date=20 April 2020}}</ref><ref name="FDA PR" /> Symptoms of capillary leak syndrome include difficulty breathing, weight gain, hypotension, or swelling of arms, legs and/or face.<ref name="FDA PR" /> The boxed warning also notes the risk of hemolytic uremic syndrome, a condition caused by the abnormal destruction of red blood cells.<ref name="Lumoxiti FDA label" /><ref name="FDA PR" /> |
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Other serious warnings include: decreased renal function, infusion-related reactions and electrolyte abnormalities.<ref name="Lumoxiti FDA label" /><ref name="FDA PR" /> |
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Women who are breastfeeding should not be given moxetumomab pasudotox.<ref name="Lumoxiti FDA label" /><ref name="FDA PR" /><ref name="Drugs.com pregnancy" /> |
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== Discovery and ownership background == |
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On 1 November 2005, ] (CAT) announced it was acquiring two ] products from ], namely GCR-3888 and GCR-8015.<ref name="prnewswire.com">{{cite press release |url=https://www.biospace.com/article/releases/cambridge-antibody-technology-group-plc-acquires-oncology-product-candidates-from-genencor-international-inc-/ |title=Cambridge Antibody Technology Acquires Oncology Product Candidates from Genencor |publisher=Cambridge Antibody Technology |access-date=12 May 2010}}</ref> Genencor is the ] division of ]<ref>{{cite web |title=Genencor |url=http://www.danisco.com/cms/connect/corporate/about+danisco/organisation/divisions/genencor/genencor_en.htm |access-date=12 August 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090107000935/http://www.danisco.com/cms/connect/corporate/about+danisco/organisation/divisions/genencor/genencor_en.htm |archive-date=7 January 2009 }}</ref> and the acquisition meant CAT would hire certain former Genencor key employees to be responsible for the development of the programmes.<ref>{{Cite web |url=http://www.danisco.com/cms/connect/corporate/media%20relations/news/archive/2005/november/investor_182_en.htm |title=Investor News |access-date=17 May 2013 |archive-url=https://archive.today/20130120085931/http://www.danisco.com/cms/connect/corporate/media%20relations/news/archive/2005/november/investor_182_en.htm |archive-date=20 January 2013 |url-status=dead }}</ref> |
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GCR-3888 and GCR-8015 were discovered and initially developed by the ], which is part of the U.S. ]. Genencor licensed the candidates for ] and entered into a ] (CRADA) with the NIH, which will now be continued by CAT. Under the original |
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license agreement with the NIH, CAT gained the rights to a portfolio of intellectual property associated with the programs and would pay future royalties to the NIH. |
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CAT intended to file an ] (IND) application for GCR-8015 in various CD22 positive B-cell malignancies, including ] and ], following a period of manufacturing development which is expected to be complete by the end of 2006 and to support the NCI's ongoing development of GCR-3888 in ] (HCL) and pediatric ] (pALL).<ref name="prnewswire.com"/> |
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CAT-8015 exhibited a greater affinity for CD22 than its predecessor, CAT-3888<ref>{{cite web|url=http://press.nci.nih.gov/Templates/drugdictionary.aspx?CdrID=540032 |archive-url=https://archive.today/20120712113209/http://press.nci.nih.gov/Templates/drugdictionary.aspx?CdrID=540032 |url-status=dead |archive-date=12 July 2012 |title=News Releases - National Cancer Institute |publisher=Press.nci.nih.gov |access-date=12 May 2010}}</ref> and CAT's language such as "CAT will support the NCI's ongoing development of CAT-3888..." suggested at the time that their focus was on the second generation candidate.<ref>{{cite web |url=http://goliath.ecnext.com/coms2/gi_0199-4981435/Cambridge-Antibody-Technology-Announces-Preliminary.html |title=Cambridge Antibody Technology Announces Preliminary Results for the Year Ended 30 September 2005. | Goliath Business News |publisher=Goliath.ecnext.com |access-date=12 May 2010 |archive-date=31 October 2021 |archive-url=https://web.archive.org/web/20211031111528/https://www.manta.com/ |url-status=dead }}</ref> |
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CAT was acquired by ], who also acquired MedImmune, combining the two into a biologics division. MedImmune renamed CAT-8015 to moxetumomab pasudotox.<ref>{{cite web | work = Statement on a Nonproprietary Name Adopted by the USAN Council | title = USAN Moxetumomab Pasudotox | publisher = American Medical Association | url = https://searchusan.ama-assn.org/usan/documentDownload?uri=/unstructured/binary/usan/moxetumomab-pasudotox.pdf }}</ref><ref>{{Cite web |url=http://www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=5997 |title=New Drugs Online Report for moxetumomab pasudotox | work = Uk Medicines Information |access-date=17 May 2013 |archive-url=https://web.archive.org/web/20160303221728/http://www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=5997 |archive-date=3 March 2016 |url-status=dead }}</ref> |
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On 16 May 2013, AstraZeneca announced that CAT-8015 had started Phase III clinical trials.<ref name="bloomberg.com">{{cite news | vauthors = Connolly A | date = 16 May 2013 | work = Bloomberg | title = AstraZeneca Advances Three Cancer Drugs Into Late-Stage Trials | url = https://www.bloomberg.com/news/2013-05-16/astrazeneca-advances-three-cancer-drugs-into-late-stage-trials.html }}</ref><ref>{{Cite news | url=https://www.reuters.com/article/us-cancer-astrazeneca-idUSBRE94F0DU20130516 |title = AstraZeneca accelerates cancer drug testing|publisher = Reuters|date = 16 May 2013}}</ref> |
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== History == |
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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.<ref name="EU/3/08/592">{{cite web | title=EU/3/08/592 | website=European Medicines Agency | date=5 December 2008 | url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu308592 | access-date=20 April 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> It was renamed to Moxetumomab pasudotox.<ref name="EU/3/08/592" /> The sponsorship was transferred to AstraZeneca AB, Sweden, in January 2019.<ref name="EU/3/08/592" /> |
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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.<ref name="EU/3/13/1150">{{cite web | title=EU/3/13/1150 | website=European Medicines Agency | date=17 July 2013 | url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3131150 | access-date=20 April 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The sponsorship was transferred to AstraZeneca AB, Sweden, in January 2019.<ref name="EU/3/13/1150" /> |
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Moxetumomab pasudotox was approved for use in the United States in September 2018.<ref name="FDA PR">{{cite press release | title=FDA approves new kind of treatment for hairy cell leukemia | website=U.S. ] (FDA) | date=13 September 2018 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-kind-treatment-hairy-cell-leukemia | access-date=20 April 2020}} {{PD-notice}}</ref> |
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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.<ref name="FDA PR" /> The trial measured durable complete response (CR), defined as maintenance of hematologic remission for more than 180 days after achievement of CR.<ref name="FDA PR" /> 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.<ref name="FDA PR" /> |
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The US ] (FDA) granted the application for moxetumomab pasudotox ], ], and ] designations.<ref name="FDA PR" /><ref>{{cite web | title=Moxetumomab pasudotox-tdfk Orphan Drug Designation and Approval | website=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=248707 | access-date=20 April 2020}}</ref> The FDA granted the approval of a Biologics License Application for Lumoxiti to AstraZeneca Pharmaceuticals.<ref name="FDA PR" /> This was subsequently transferred to Innate Pharma in March 2020.<ref>{{cite letter | vauthors = Gormley N | work = Center for Drug Evaluation and Research | publisher = U.S. Food and Drug Administration |subject = Supplemental biologics license application (sBLA) for LUMOXITI (moxetumomab pasudotox-tdfk) for injection | recipient = David Lucking (Innate Pharma, Inc.) | url = https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/761104Orig1s003ltr.pdf}}</ref> |
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On 10 December 2020, the ] (CHMP) of the ] (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.<ref>{{cite web | title=Lumoxiti: Pending EC decision | website=] (EMA) | date=10 December 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/lumoxiti | access-date=11 December 2020 | archive-date=11 December 2020 | archive-url=https://web.archive.org/web/20201211165541/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/lumoxiti | url-status=dead }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The applicant for this medicinal product is AstraZeneca AB. Moxetumomab pasudotox was approved for medical use in the European Union in February 2021.<ref name="Lumoxiti EPAR">{{cite web | title=Lumoxiti EPAR | website=] (EMA) | date=9 December 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lumoxiti | access-date=1 May 2021}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The EU marketing authorization was withdrawn in July 2021.<ref name="Lumoxiti EPAR" /> |
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== References == |
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{{reflist}} |
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== External links == |
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{{monoclonals for tumors}} |
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* {{cite web | title=Moxetumomab Pasudotox-tdfk | website=National Cancer Institute | date=24 October 2018 | url=https://www.cancer.gov/about-cancer/treatment/drugs/moxetumomabpasudotoxtdfk }} |
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* {{cite web | title=Moxetumomab Pasudotox-tdfk | work=NCI Drug Dictionary | publisher=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug }} |
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{{Targeted cancer therapeutic agents}} |
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{{Monoclonals for tumors}} |
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{{Portal bar | Medicine}} |
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] |
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{{monoclonal-antibody-stub}} |
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{{antineoplastic-drug-stub}} |
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