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{{Short description|Medication used to treat chronic lymphocytic leukemia (CLL)}}
{{Short description|Medication}}
{{Use dmy dates|date=December 2023}}
{{Drugbox
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
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| Drugs.com = {{drugs.com|monograph|alemtuzumab}}
| Drugs.com = {{drugs.com|monograph|alemtuzumab}}
| MedlinePlus = a608053
| MedlinePlus = a608053
| licence_EU = yes
| DailyMedID = Alemtuzumab
| DailyMedID = Alemtuzumab
| pregnancy_AU = B3
| pregnancy_AU = B3
| pregnancy_AU_comment = (Lemtrada); B2 (Mabcampath)<ref>{{cite web | title=Alemtuzumab Use During Pregnancy | website=Drugs.com | date=22 August 2022 | url=https://www.drugs.com/pregnancy/alemtuzumab.html | access-date=6 January 2024}}</ref><ref>{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-02549-1 | title=TGA eBS - Product and Consumer Medicine Information Licence }}</ref><ref>{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-01413-3 | title=TGA eBS - Product and Consumer Medicine Information Licence }}</ref>
| pregnancy_AU_comment = (Lemtrada); B2 (Mabcampath)
| routes_of_administration = [[Intravenous infusion]]
| routes_of_administration = [[Intravenous infusion]]
| ATC_prefix = L04 <!-- scheduled to be L04AG06 in 2024 -->
| ATC_prefix = L04
| ATC_suffix = AA34
| ATC_suffix = AG06
| ATC_supplemental =
| ATC_supplemental =


| legal_AU = S4
| legal_AU = S4
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| legal_UK = POM
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Campath FDA label">{{cite web | title=Campath- alemtuzumab injection | website=DailyMed | date=3 May 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4f5f7255-7abc-4328-bd1a-ceaf139ef3e0 | access-date=6 January 2024}}</ref><ref name="Lemtrada FDA label">{{cite web | title=Lemtrada- alemtuzumab injection, solution, concentrate | website=DailyMed | date=23 May 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6236b0bc-82e9-4447-9a78-f57d94770269 | access-date=6 January 2024}}</ref>
| legal_EU = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | website=European Medicines Agency | title=Lemtrada EPAR | date=12 September 2013 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lemtrada | access-date=6 January 2024}}</ref>
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| legal_UK = POM


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<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Alemtuzumab''', sold under the brand names '''Campath''' and '''Lemtrada''' among others, is a [[medication]] used to treat [[chronic lymphocytic leukemia]] (CLL) and [[multiple sclerosis]].<ref name=AHFS2019>{{cite web |title=Alemtuzumab Monograph for Professionals |url=https://www.drugs.com/monograph/alemtuzumab.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=15 July 2019 |language=en}}</ref> In CLL, it has been used as both a first line and second line treatment.<ref name=AHFS2019/> In MS it is generally only recommended if other treatments have not worked.<ref name=AHFS2019/> It is given by [[injection into a vein]].<ref name=AHFS2019/>
'''Alemtuzumab''', sold under the brand names '''Campath''' and '''Lemtrada''' among others, is a [[medication]] used to treat [[chronic lymphocytic leukemia]] and [[multiple sclerosis]].<ref name=AHFS2019>{{cite web |title=Alemtuzumab Monograph for Professionals |url=https://www.drugs.com/monograph/alemtuzumab.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=15 July 2019 }}</ref> In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment.<ref name=AHFS2019/> It is given by [[injection into a vein]].<ref name=AHFS2019/>


It is a [[monoclonal antibody]] that binds to [[CD52]], a protein present on the surface of mature [[lymphocyte]]s, but not on the [[stem cell]]s from which these lymphocytes are derived. After treatment with alemtuzumab, these CD52-bearing lymphocytes are targeted for destruction.
It is a [[monoclonal antibody]] that binds to [[CD52]], a protein present on the surface of mature [[lymphocyte]]s, but not on the [[stem cell]]s from which these lymphocytes are derived. After treatment with alemtuzumab, these CD52-bearing lymphocytes are targeted for destruction.


Alemtuzumab was approved for medical use in the United States in 2001.<ref name=AHFS2019/> (Mab)Campath was withdrawn from the markets in the US and Europe in 2012, to prepare for a higher-priced relaunch of Lemtrada aimed at multiple sclerosis.<ref name=pt/>
Alemtuzumab was approved for medical use in the United States in 2001.<ref name=AHFS2019/> (Mab)Campath was withdrawn from the markets in the US and the EU in 2012, to prepare for a higher-priced relaunch of Lemtrada aimed at multiple sclerosis.<ref name=pt/>


== Medical uses ==
== Medical uses ==


===Chronic lymphocytic leukemia===
===Chronic lymphocytic leukemia===
Alemtuzumab is used for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in people who have been treated with alkylating agents and who have failed fludarabine therapy. It is an unconjugated antibody, thought to work via the activation of [[antibody-dependent cell-mediated cytotoxicity]] (ADCC).<ref>{{cite web|url=http://www.campath.com/hcp/AboutCampath.html |title=About Campath |publisher=Genzyme |url-status=dead |archive-url=https://web.archive.org/web/20110714063804/http://www.campath.com/hcp/AboutCampath.html |archive-date=2011-07-14 }}</ref>
Alemtuzumab is used for the treatment of B-cell chronic lymphocytic leukemia in people who have been treated with alkylating agents and who have failed [[fludarabine]] therapy. It is an unconjugated antibody, thought to work via the activation of [[antibody-dependent cell-mediated cytotoxicity]].<ref>{{cite web|url=http://www.campath.com/hcp/AboutCampath.html |title=About Campath |publisher=Genzyme |url-status=dead |archive-url=https://web.archive.org/web/20110714063804/http://www.campath.com/hcp/AboutCampath.html |archive-date=2011-07-14 }}</ref>{{Unreliable medical source|date=January 2024}}


===Multiple sclerosis===
===Multiple sclerosis===
It is used for the relapsing remitting form of multiple sclerosis.<ref name=AHFS2019/> A 2017 Cochrane meta-analysis of studies comparing alemtuzumab to interferon beta 1a concluded that annual cycles of alemtuzumab probably reduces the proportion of people that experience relapse and may reduce the proportion of people who experience disability worsening and new T2 lesions on MRI, with adverse events found to be similarly high for both treatments.<ref name=":0">{{cite journal | vauthors = Zhang J, Shi S, Zhang Y, Luo J, Xiao Y, Meng L, Yang X | title = Alemtuzumab versus interferon beta 1a for relapsing-remitting multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 5 | pages = CD010968 | date = November 2017 | pmid = 29178444 | pmc = 6486233 | doi = 10.1002/14651858.CD010968.pub2 }}</ref> However the low-to-moderate levels of evidence in the included, existing studies were noted and the need for larger high-quality randomised, double‐blind, controlled trials comparing mono or combination therapy with alemtuzumab was highlighted.<ref name=":0" /> It is generally only recommended in people do not respond sufficiently to at least two other MS medications.<ref name=AHFS2019/>
It is used for the relapsing remitting form of multiple sclerosis.<ref name=AHFS2019/> A 2017 Cochrane meta-analysis of studies comparing alemtuzumab to interferon beta 1a concluded that annual cycles of alemtuzumab probably reduces the proportion of people that experience relapse and may reduce the proportion of people who experience disability worsening and new T2 lesions on MRI, with adverse events found to be similarly high for both treatments.<ref name=":0">{{cite journal | vauthors = Zhang J, Shi S, Zhang Y, Luo J, Xiao Y, Meng L, Yang X | title = Alemtuzumab versus interferon beta 1a for relapsing-remitting multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD010968 | date = November 2017 | pmid = 29178444 | pmc = 6486233 | doi = 10.1002/14651858.CD010968.pub2 }}</ref> However the low-to-moderate levels of evidence in the included, existing studies were noted and the need for larger high-quality randomised, double-blind, controlled trials comparing mono or combination therapy with alemtuzumab was highlighted.<ref name=":0" />


== Contraindications ==
== Contraindications ==
Alemtuzumab is contraindicated in patients who have active infections, underlying immunodeficiency (e.g., seropositive for HIV), or known type I hypersensitivity or anaphylactic reactions to the substance.<ref>{{cite web |title=LEMTRADA® (alemtuzumab) injection, for intravenous use Prescribing Information |url=https://products.sanofi.us/lemtrada/lemtrada.html |website=products.sanofi.us |access-date=11 October 2021}}</ref>
Alemtuzumab is contraindicated in patients who have active infections, underlying immunodeficiency (e.g., seropositive for HIV), or known type I hypersensitivity or anaphylactic reactions to the substance.<ref name="Lemtrada FDA label" />


== Adverse effects==
== Adverse effects==
In November 2018, the US [[Food and Drug Administration]] (FDA) issued a Safety Announcement<ref>{{cite web | title = FDA warns about rare but serious risks of stroke and blood vessel wall tears with multiple sclerosis drug Lemtrada (alemtuzumab) | work = FDA Drug Safety Communication | publisher = U.S. Food and Drug Administration | date = 29 November 2018 | url = https://www.fda.gov/downloads/Drugs/DrugSafety/UCM626584.pdf}}</ref> warning about rare but serious instances of stroke and blood vessel wall tears in multiple sclerosis patients who have received Lemtrada (alemtuzumab), mostly occurring within 1 day of initiating treatment and leading in some cases to permanent disability and even death.
In November 2018, the US [[Food and Drug Administration]] (FDA) issued a safety announcement<ref>{{cite web | title = FDA warns about rare but serious risks of stroke and blood vessel wall tears with multiple sclerosis drug Lemtrada (alemtuzumab) | work = FDA Drug Safety Communication | publisher = U.S. [[Food and Drug Administration]] (FDA) | date = 29 November 2018 | url = https://www.fda.gov/media/118875/download }}</ref> warning about rare but serious instances of stroke and blood vessel wall tears in multiple sclerosis patients who have received Lemtrada (alemtuzumab), mostly occurring within one day of initiating treatment and leading in some cases to permanent disability and even death.


In addition to the 13 cases to which the FDA Safety Announcement refers, a further 5 cases of spontaneous intracranial haemorrhage have been retrospectively identified from four US multiple sclerosis centres in correspondence published online in February 2019.<ref>{{cite journal | vauthors = Azevedo CJ, Kutz C, Dix A, Boster A, Sanossian N, Kaplan J | title = Intracerebral haemorrhage during alemtuzumab administration | journal = The Lancet. Neurology | volume = 18 | issue = 4 | pages = 329–331 | date = April 2019 | pmid = 30777657 | doi = 10.1016/S1474-4422(19)30076-6 | doi-access = free }}</ref>
In addition to the 13 cases to which the FDA safety announcement refers, a further five cases of spontaneous intracranial hemorrhage have been retrospectively identified from four US multiple sclerosis centers in correspondence published online in February 2019.<ref>{{cite journal | vauthors = Azevedo CJ, Kutz C, Dix A, Boster A, Sanossian N, Kaplan J | title = Intracerebral haemorrhage during alemtuzumab administration | journal = The Lancet. Neurology | volume = 18 | issue = 4 | pages = 329–331 | date = April 2019 | pmid = 30777657 | doi = 10.1016/S1474-4422(19)30076-6 | s2cid = 72334305 }}</ref>


On 12 April 2019, the [https://www.ema.europa.eu/en/committees/pharmacovigilance-risk-assessment-committee-prac Pharmacovigilance Risk Assessment Committee] (PRAC) of the [[European Medicines Agency]] (EMA) reported that it has started a review of the multiple sclerosis medicine Lemtrada (alemtuzumab) following new reports of immune-mediated conditions and of problems with the heart and blood vessels with this medicine, including fatal cases. PRAC advised that while the review is ongoing, Lemtrada should only be started in adults with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease-modifying therapies (a type of multiple sclerosis medicine) or where other disease-modifying therapies cannot be used. PRAC further advised that patients being treated with Lemtrada who are benefitting from it may continue treatment in consultation with their doctor.<ref>{{cite web | title = Use of multiple sclerosis medicine Lemtrada restricted while PRAC review is ongoing | work = Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) | publisher = European Medicines Agency | date = 12 April 2019 | url = https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-8-11-april-2019}}</ref>
In April 2019, the [https://www.ema.europa.eu/en/committees/pharmacovigilance-risk-assessment-committee-prac Pharmacovigilance Risk Assessment Committee] (PRAC) of the [[European Medicines Agency]] (EMA) reported that it has started a review of the multiple sclerosis medicine Lemtrada (alemtuzumab) following new reports of immune-mediated conditions and of problems with the heart and blood vessels with this medicine, including fatal cases. The PRAC advised that while the review is ongoing, Lemtrada should only be started in adults with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease-modifying therapies (a type of multiple sclerosis medicine) or where other disease-modifying therapies cannot be used. The PRAC further advised that patients being treated with Lemtrada who are benefitting from it may continue treatment in consultation with their doctor.<ref>{{cite web | title = Use of multiple sclerosis medicine Lemtrada restricted while PRAC review is ongoing | work = Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) | publisher = European Medicines Agency | date = 12 April 2019 | url = https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-8-11-april-2019}}</ref>


Very common adverse reactions associated with alemtuzumab infusion in MS patients include upper respiratory tract and urinary tract infections, herpes virus infections, lymphopenia, leucopenia, changes in thyroid function, tachycardia, skin rashes, pruritus, pyrexia, and fatigue.<ref>{{Cite web|url=https://www.medicines.org.uk/emc/product/5409#UNDESIRABLE_EFFECTS|title = LEMTRADA 12 mg concentrate for solution for infusion - Summary of Product Characteristics (SMPC) - (Emc)}}</ref> The Summary of Product Characteristics provided in the electronic Medicines Compendium [eMC <ref>{{Cite web|url=https://www.medicines.org.uk/emc/|title=Home - electronic medicines compendium (Emc)}}</ref>] further lists common and uncommon adverse reactions that have been reported for Lemtrada, which include serious opportunistic nocardial infections and cytomegalovirus syndrome.<ref name=Sheikh-Taha2017>{{cite journal | vauthors = Sheikh-Taha M, Corman LC | title = Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis | journal = Multiple Sclerosis | volume = 23 | issue = 6 | pages = 872–874 | date = May 2017 | pmid = 28290754 | doi = 10.1177/1352458517694431 | s2cid = 206702778 }}</ref><ref name=Clerico2017>{{cite journal | vauthors = Clerico M, De Mercanti S, Artusi CA, Durelli L, Naismith RT | title = Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab | journal = Multiple Sclerosis | volume = 23 | issue = 6 | pages = 874–876 | date = May 2017 | pmid = 28290755 | doi = 10.1177/1352458516688350 | s2cid = 206702649 }}</ref><ref name=Brownlee2017>{{cite journal | vauthors = Brownlee WJ, Chataway J | title = Opportunistic infections after alemtuzumab: New cases of norcardial infection and cytomegalovirus syndrome | journal = Multiple Sclerosis | volume = 23 | issue = 6 | pages = 876–877 | date = May 2017 | pmid = 28290753 | doi = 10.1177/1352458517693440 | s2cid = 30519152 | url = https://discovery.ucl.ac.uk/id/eprint/1537542/ }}</ref>
Very common adverse reactions associated with alemtuzumab infusion in people with multiple sclerosis include upper respiratory tract and urinary tract infections, herpes virus infections, lymphopenia, leucopenia, changes in thyroid function, tachycardia, skin rashes, pruritus, pyrexia, and fatigue.<ref>{{cite web|url=https://www.medicines.org.uk/emc/product/5409#UNDESIRABLE_EFFECTS|title=LEMTRADA 12 mg concentrate for solution for infusion - Summary of Product Characteristics (SMPC) - (Emc)|access-date=7 April 2019|archive-date=6 May 2021|archive-url=https://web.archive.org/web/20210506131642/https://www.medicines.org.uk/emc/product/5409#UNDESIRABLE_EFFECTS|url-status=dead}}</ref> The Summary of Product Characteristics provided in the electronic Medicines Compendium [eMC <ref>{{Cite web|url=https://www.medicines.org.uk/emc/|title=Home - electronic medicines compendium (emc)|website=www.medicines.org.uk|accessdate=16 February 2024}}</ref>] further lists common and uncommon adverse reactions that have been reported for Lemtrada, which include serious opportunistic nocardial infections and cytomegalovirus syndrome.<ref name=Sheikh-Taha2017>{{cite journal | vauthors = Sheikh-Taha M, Corman LC | title = Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis | journal = Multiple Sclerosis | volume = 23 | issue = 6 | pages = 872–874 | date = May 2017 | pmid = 28290754 | doi = 10.1177/1352458517694431 | s2cid = 206702778 }}</ref><ref name=Clerico2017>{{cite journal | vauthors = Clerico M, De Mercanti S, Artusi CA, Durelli L, Naismith RT | title = Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab | journal = Multiple Sclerosis | volume = 23 | issue = 6 | pages = 874–876 | date = May 2017 | pmid = 28290755 | doi = 10.1177/1352458516688350 | s2cid = 206702649 }}</ref><ref name=Brownlee2017>{{cite journal | vauthors = Brownlee WJ, Chataway J | title = Opportunistic infections after alemtuzumab: New cases of norcardial infection and cytomegalovirus syndrome | journal = Multiple Sclerosis | volume = 23 | issue = 6 | pages = 876–877 | date = May 2017 | pmid = 28290753 | doi = 10.1177/1352458517693440 | s2cid = 30519152 | url = https://discovery.ucl.ac.uk/id/eprint/1537542/ }}</ref>


Alemtuzumab can also precipitate [[autoimmune disease]] through the suppression of [[regulatory T cell]] populations and/or the emergence of autoreactive B-cells.<ref name=Costelloe2012>{{cite journal | vauthors = Costelloe L, Jones J, Coles A | title = Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis | journal = Expert Review of Neurotherapeutics | volume = 12 | issue = 3 | pages = 335–341 | date = March 2012 | pmid = 22364332 | doi = 10.1586/ern.12.5 | s2cid = 34738692 }}</ref><ref name=Aranha2013>{{cite journal | vauthors = Aranha AA, Amer S, Reda ES, Broadley SA, Davoren PM | title = Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review | journal = Endocrine Practice | volume = 19 | issue = 5 | pages = 821–828 | date = 2013 | pmid = 23757618 | doi = 10.4158/EP13020.RA }}</ref>
Alemtuzumab can also precipitate [[autoimmune disease]] through the suppression of [[regulatory T cell]] populations and/or the emergence of autoreactive B-cells.<ref name=Costelloe2012>{{cite journal | vauthors = Costelloe L, Jones J, Coles A | title = Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis | journal = Expert Review of Neurotherapeutics | volume = 12 | issue = 3 | pages = 335–341 | date = March 2012 | pmid = 22364332 | doi = 10.1586/ern.12.5 | s2cid = 34738692 }}</ref><ref name=Aranha2013>{{cite journal | vauthors = Aranha AA, Amer S, Reda ES, Broadley SA, Davoren PM | title = Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review | journal = Endocrine Practice | volume = 19 | issue = 5 | pages = 821–828 | date = 2013 | pmid = 23757618 | doi = 10.4158/EP13020.RA }}</ref>


Cases of multiple sclerosis reactivation/relapse have also been reported<ref>{{cite journal | vauthors = Wehrum T, Beume LA, Stich O, Mader I, Mäurer M, Czaplinski A, Weiller C, Rauer S | display-authors = 6 | title = Activation of disease during therapy with alemtuzumab in 3 patients with multiple sclerosis | journal = Neurology | volume = 90 | issue = 7 | pages = e601–e605 | date = February 2018 | pmid = 29352101 | doi = 10.1212/WNL.0000000000004950 | s2cid = 3319939 }}</ref>
Cases of multiple sclerosis reactivation/relapse have also been reported<ref>{{cite journal | vauthors = Wehrum T, Beume LA, Stich O, Mader I, Mäurer M, Czaplinski A, Weiller C, Rauer S | title = Activation of disease during therapy with alemtuzumab in 3 patients with multiple sclerosis | journal = Neurology | volume = 90 | issue = 7 | pages = e601–e605 | date = February 2018 | pmid = 29352101 | doi = 10.1212/WNL.0000000000004950 | s2cid = 3319939 }}</ref>


== Biochemical properties ==
== Biochemical properties ==
Alemtuzumab is a recombinant DNA-derived humanized [[IgG1]] kappa monoclonal antibody that is directed against the cell surface glycoprotein [[CD52]].<ref name="Klement">{{cite journal| author = A. Klement| date = 7 January 2014| title = Multiple-Sklerose-Behandlung| journal = Österreichische Apothekerzeitung| issue = 1/2014| page = 24f| language = de}}</ref>
Alemtuzumab is a recombinant DNA-derived humanized [[IgG1]] kappa monoclonal antibody that is directed against the cell surface glycoprotein [[CD52]].<ref name="Klement">{{cite journal| vauthors = Klement A | date = 7 January 2014| title = Multiple-Sklerose-Behandlung| journal = Österreichische Apothekerzeitung| issue = 1/2014| page = 24f| language = de}}</ref>

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===Antiviral properties===
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In an in-vitro experiment, it has been shown that alemtuzumab has antiviral properties against [[HIV-1]].<ref>{{cite journal | vauthors = Ruxrungtham K, Sirivichayakul S, Buranapraditkun S, Krause W | title = Alemtuzumab-induced elimination of HIV-1-infected immune cells | journal = Journal of Virus Eradication | volume = 2 | issue = 1 | pages = 12–18 | date = January 2016 | pmid = 27482429 | pmc = 4946689 | doi = 10.1016/S2055-6640(20)30694-4 }}</ref>


== History ==
== History ==
The origins of alemtuzumab date back to ''Campath-1'' which was derived from the rat antibodies raised against human lymphocyte proteins by [[Herman Waldmann]] and colleagues in 1983.<ref>{{cite journal | vauthors = Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H | title = Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement | journal = Blood | volume = 62 | issue = 4 | pages = 873–882 | date = October 1983 | pmid = 6349718 | doi = 10.1182/blood.V62.4.873.873 | doi-access = free }}</ref> The name "Campath" derives from the ''path''ology department of [[University of Cambridge|Cambridge University]].
The origins of alemtuzumab date back to Campath-1 which was derived from the rat antibodies raised against human lymphocyte proteins by [[Herman Waldmann]] and colleagues in 1983.<ref>{{cite journal | vauthors = Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H | title = Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement | journal = Blood | volume = 62 | issue = 4 | pages = 873–882 | date = October 1983 | pmid = 6349718 | doi = 10.1182/blood.V62.4.873.873 | doi-access = free | title-link = doi }}</ref> The name Campath derives from the ''path''ology department of [[University of Cambridge|Cambridge University]].


Initially, Campath-1 was not ideal for therapy because patients could, in theory, react against the foreign rat protein determinants of the antibody. To circumvent this problem, [[Greg Winter]] and his colleagues humanised Campath-1, by extracting the [[Complementarity-determining region|hypervariable loops]] that had specificity for CD52 and grafting them onto a human antibody framework. This became known as Campath-1H and serves as the basis for alemtuzumab.<ref name=pmid3127726>{{cite journal | vauthors = Riechmann L, Clark M, Waldmann H, Winter G | title = Reshaping human antibodies for therapy | journal = Nature | volume = 332 | issue = 6162 | pages = 323–327 | date = March 1988 | pmid = 3127726 | doi = 10.1038/332323a0 | s2cid = 4335569 | bibcode = 1988Natur.332..323R }}</ref>
Initially, Campath-1 was not ideal for therapy because patients could, in theory, react against the foreign rat protein determinants of the antibody. To circumvent this problem, [[Greg Winter]] and his colleagues humanised Campath-1, by extracting the [[Complementarity-determining region|hypervariable loops]] that had specificity for CD52 and grafting them onto a human antibody framework. This became known as Campath-1H and serves as the basis for alemtuzumab.<ref name=pmid3127726>{{cite journal | vauthors = Riechmann L, Clark M, Waldmann H, Winter G | title = Reshaping human antibodies for therapy | journal = Nature | volume = 332 | issue = 6162 | pages = 323–327 | date = March 1988 | pmid = 3127726 | doi = 10.1038/332323a0 | s2cid = 4335569 | doi-access = free | title-link = doi | bibcode = 1988Natur.332..323R }}</ref>


While alemtuzumab started life as a laboratory tool for understanding the immune system, within a short time it was clinically investigated for use to improve the success of bone marrow transplants and as a treatment for leukaemia, lymphoma, vasculitis, organ transplants, rheumatoid arthritis and multiple sclerosis.<ref>{{cite web|url=http://www.whatisbiotechnology.org/exhibitions/campath|title=The life story of a biotechnology drug: Alemtuzumab|publisher=What is Biotechnology?}}</ref>
While alemtuzumab started life as a laboratory tool for understanding the immune system, within a short time it was clinically investigated for use to improve the success of bone marrow transplants and as a treatment for leukaemia, lymphoma, vasculitis, organ transplants, rheumatoid arthritis and multiple sclerosis.<ref>{{cite web|url=http://www.whatisbiotechnology.org/exhibitions/campath|title=The life story of a biotechnology drug: Alemtuzumab|publisher=What is Biotechnology?}}</ref>


== Society and culture ==
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Campath as medication was first approved for B-cell chronic lymphocytic leukemia in 2001. It is marketed by [[Genzyme]], which acquired the worldwide rights from [[Bayer AG]] in 2009. Genzyme was bought by [[Sanofi]] in 2011. In August/September 2012 Campath was withdrawn from the markets in the US and Europe. This was done to prevent [[off-label use]] of the drug to treat multiple sclerosis and to prepare for a relaunch under the trade name ''Lemtrada'', with a different dosage aimed at multiple sclerosis treatment, this is expected to be much higher-priced.<ref name=pt>{{cite news | title=Sanofi withdraws Campath in US and EU | author=McKee, Selina | date=21 August 2012 | work=Pharma Times Online | publisher=Pharma Times | url=http://www.pharmatimes.com/Article/12-08-21/Sanofi_withdraws_Campath_in_US_and_EU.aspx }}</ref>
=== Economics ===
⚫
Campath as a medication was first approved for B-cell chronic lymphocytic leukemia in 2001. It is marketed by [[Genzyme]], which acquired the worldwide rights from [[Bayer AG]] in 2009. Genzyme was bought by [[Sanofi]] in 2011. In August/September 2012 Campath was withdrawn from the markets in the US and EU. This was done to prevent [[off-label use]] of the drug to treat multiple sclerosis and to prepare for a relaunch under the brand name Lemtrada, with a different dosage aimed at multiple sclerosis treatment, this is expected to be much higher-priced.<ref name=pt>{{cite news | title=Sanofi withdraws Campath in US and EU | vauthors=McKee S | date=21 August 2012 | work=Pharma Times Online | publisher=Pharma Times | url=http://www.pharmatimes.com/Article/12-08-21/Sanofi_withdraws_Campath_in_US_and_EU.aspx | access-date=6 November 2012 | archive-date=4 March 2016 | archive-url=https://web.archive.org/web/20160304031613/http://www.pharmatimes.com/Article/12-08-21/Sanofi_withdraws_Campath_in_US_and_EU.aspx | url-status=dead }}</ref>


⚫
In February 2011, Sanofi-Aventis, since renamed [[Sanofi]], acquired Genzyme, the manufacturer of alemtuzumab.<ref>{{cite news | title=Sanofi Buys Genzyme for over $20 billion | date=17 February 2011 | vauthors = Whalen J, Spencer M | url=https://www.wsj.com/articles/SB10001424052748703373404576147483489656732 | work=[[The Wall Street Journal]] | url-access = subscription}}</ref> The acquisition was delayed by a dispute between the two companies regarding the value of alemtuzumab.
Bayer reserves the right to co-promote Lemtrada for 5 years, with the option to renew for an additional five years.


⚫
In August 2012, Genzyme surrendered the license for all presentations of alemtuzumab,<ref>{{cite web | title=Discontinuation of licensed supplies of alemtuzumab (Mabcampath) | vauthors = Hussein J | url = http://www.medicinesresources.nhs.uk/upload/documents/News/2012/Sanofil%20letter.pdf | publisher=National Institute for Health and Care Excellence | location=United Kingdom | date=9 August 2012 }}</ref> pending regulatory approval to reintroduce it as a treatment for [[multiple sclerosis]]. Concerns<ref>{{cite news|title=Multiple sclerosis: New drug 'most effective'|url=https://www.bbc.co.uk/news/health-20151891|access-date=1 November 2012|newspaper=BBC News|date=1 November 2012}}</ref> that Genzyme would later bring to market the same product at a much higher price proved correct.
=== Sanofi acquisition and change of license controversy===
⚫
In February 2011, Sanofi-Aventis, since renamed [[Sanofi]], acquired Genzyme, the manufacturer of alemtuzumab.<ref>{{cite news | title=Sanofi Buys Genzyme for over $20 billion | date=17 February 2011 | author=Whalen, Jeanne | author2=Spencer, Mimosa | url=https://www.wsj.com/articles/SB10001424052748703373404576147483489656732 | work=[[The Wall Street Journal]] }}{{paywall}}</ref> The acquisition was delayed by a dispute between the two companies regarding the value of alemtuzumab. The dispute was settled by the issuance of Contingent Value Rights, a type of stock warrant which pays a dividend only if alemtuzumab reaches certain sales targets. The contingent value rights (CVR) trade on the NASDAQ-GM market with the ticker symbol GCVRZ.


=== Names ===
⚫
In August 2012, Genzyme surrendered the licence for all presentations of alemtuzumab,<ref>{{cite web | title=Discontinuation of licensed supplies of alemtuzumab (Mabcampath) | author=Hussein, Jasmin (Genzyme) | url=http://www.medicinesresources.nhs.uk/upload/documents/News/2012/Sanofil%20letter.pdf | publisher=National Institute for Health and Care Excellence | location=United Kingdom | date=9 August 2012 }}</ref> pending regulatory approval to re-introduce it as a treatment for [[multiple sclerosis]]. Concerns<ref>{{cite news|title=Multiple sclerosis: New drug 'most effective'|url=https://www.bbc.co.uk/news/health-20151891|access-date=1 November 2012|newspaper=BBC News|date=1 November 2012}}</ref> that Genzyme would later bring to market the same product at a much higher price proved correct.
Alemtuzumab is the [[international nonproprietary name]].<ref>{{cite journal | vauthors = ((World Health Organization)) | year = 2023 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90 | journal = WHO Drug Information | volume = 37 | issue = 3 | hdl = 10665/373341 | hdl-access = free | author-link = World Health Organization }}</ref>


==Research and off-label use==
== Research ==

⚫
===Antiviral properties===
⚫
In an in-vitro experiment, it has been shown that alemtuzumab has antiviral properties against [[HIV-1]].<ref>{{cite journal | vauthors = Ruxrungtham K, Sirivichayakul S, Buranapraditkun S, Krause W | title = Alemtuzumab-induced elimination of HIV-1-infected immune cells | journal = Journal of Virus Eradication | volume = 2 | issue = 1 | pages = 12–18 | date = January 2016 | pmid = 27482429 | pmc = 4946689 | doi = 10.1016/S2055-6640(20)30694-4 }}</ref>


===Graft-versus-host disease===
===Graft-versus-host disease===
A 2009 retrospective study of alemtuzumab (10&nbsp;mg IV weekly) in 20 patients (no controls) with severe steroid-resistant acute intestinal [[graft-versus-host disease]] after allogeneic [[hematopoietic stem cell transplantation]] (HSCT) demonstrated improvement. Overall response rate was 70%, with complete response in 35%.<ref name=Schn2009/> In this study, the median survival was 280 days. Important complications following this treatment included [[cytomegalovirus]] reactivation, bacterial infection, and invasive [[aspergillosis]] infection.<ref name=Schn2009>{{cite journal | vauthors = Schnitzler M, Hasskarl J, Egger M, Bertz H, Finke J | title = Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab | journal = Biology of Blood and Marrow Transplantation | volume = 15 | issue = 8 | pages = 910–918 | date = August 2009 | pmid = 19589480 | doi = 10.1016/j.bbmt.2009.04.002 | doi-access = free }}{{open access}}</ref>
A 2009 retrospective study of alemtuzumab (10&nbsp;mg IV weekly) in 20 patients (no controls) with severe steroid-resistant acute intestinal [[graft-versus-host disease]] after allogeneic [[hematopoietic stem cell transplantation]] (HSCT) demonstrated improvement. Overall response rate was 70%, with complete response in 35%.<ref name=Schn2009/> In this study, the median survival was 280 days. Important complications following this treatment included [[cytomegalovirus]] reactivation, bacterial infection, and invasive [[aspergillosis]] infection.<ref name=Schn2009>{{cite journal | vauthors = Schnitzler M, Hasskarl J, Egger M, Bertz H, Finke J | title = Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab | journal = Biology of Blood and Marrow Transplantation | volume = 15 | issue = 8 | pages = 910–918 | date = August 2009 | pmid = 19589480 | doi = 10.1016/j.bbmt.2009.04.002 | doi-access = free | title-link = doi }} </ref>


== References ==
== References ==
Line 116: Line 121:


== External links ==
== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/alemtuzumab | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Alemtuzumab }}
* [http://users.path.ox.ac.uk/~scobbold/tig/CAMPATH/CAMPHIST.HTM From laboratory to clinic: the story of CAMPATH-1 (Geoff Hale and Herman Waldmann)]
* [http://users.path.ox.ac.uk/~scobbold/tig/CAMPATH/CAMPHIST.HTM From laboratory to clinic: the story of CAMPATH-1 (Geoff Hale and Herman Waldmann)]
* {{cite web | title=Alemtuzumab | website=National Cancer Institute | date=30 November 2007 | url=https://www.cancer.gov/about-cancer/treatment/drugs/alemtuzumab }}


{{Demyelinating diseases of CNS}}
{{Demyelinating diseases of CNS}}
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{{Monoclonals for tumors}}
{{Monoclonals for tumors}}
{{Portal bar | Medicine}}
{{Portal bar | Medicine}}
{{Authority control}}


[[Category:Monoclonal antibodies for tumors]]
[[Category:Monoclonal antibodies for tumors]]
[[Category:Sanofi]]
[[Category:Sanofi]]
[[Category:Withdrawn drugs]]

Latest revision as of 02:49, 24 August 2024

Alemtuzumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from rat)
TargetCD52
Clinical data
Trade namesCampath, Mabcampath, Lemtrada, others
AHFS/Drugs.comMonograph
MedlinePlusa608053
License data
Pregnancy
category
Routes of
administration		Intravenous infusion
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life~288 hrs
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6468H10066N1732O2005S40
Molar mass145454.20 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia and multiple sclerosis.[8] In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment.[8] It is given by injection into a vein.[8]

It is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. After treatment with alemtuzumab, these CD52-bearing lymphocytes are targeted for destruction.

Alemtuzumab was approved for medical use in the United States in 2001.[8] (Mab)Campath was withdrawn from the markets in the US and the EU in 2012, to prepare for a higher-priced relaunch of Lemtrada aimed at multiple sclerosis.[9]

Medical uses

[edit]

Chronic lymphocytic leukemia

[edit]

Alemtuzumab is used for the treatment of B-cell chronic lymphocytic leukemia in people who have been treated with alkylating agents and who have failed fludarabine therapy. It is an unconjugated antibody, thought to work via the activation of antibody-dependent cell-mediated cytotoxicity.[10][unreliable medical source?]

Multiple sclerosis

[edit]

It is used for the relapsing remitting form of multiple sclerosis.[8] A 2017 Cochrane meta-analysis of studies comparing alemtuzumab to interferon beta 1a concluded that annual cycles of alemtuzumab probably reduces the proportion of people that experience relapse and may reduce the proportion of people who experience disability worsening and new T2 lesions on MRI, with adverse events found to be similarly high for both treatments.[11] However the low-to-moderate levels of evidence in the included, existing studies were noted and the need for larger high-quality randomised, double-blind, controlled trials comparing mono or combination therapy with alemtuzumab was highlighted.[11]

Contraindications

[edit]

Alemtuzumab is contraindicated in patients who have active infections, underlying immunodeficiency (e.g., seropositive for HIV), or known type I hypersensitivity or anaphylactic reactions to the substance.[6]

Adverse effects

[edit]

In November 2018, the US Food and Drug Administration (FDA) issued a safety announcement[12] warning about rare but serious instances of stroke and blood vessel wall tears in multiple sclerosis patients who have received Lemtrada (alemtuzumab), mostly occurring within one day of initiating treatment and leading in some cases to permanent disability and even death.

In addition to the 13 cases to which the FDA safety announcement refers, a further five cases of spontaneous intracranial hemorrhage have been retrospectively identified from four US multiple sclerosis centers in correspondence published online in February 2019.[13]

In April 2019, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) reported that it has started a review of the multiple sclerosis medicine Lemtrada (alemtuzumab) following new reports of immune-mediated conditions and of problems with the heart and blood vessels with this medicine, including fatal cases. The PRAC advised that while the review is ongoing, Lemtrada should only be started in adults with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease-modifying therapies (a type of multiple sclerosis medicine) or where other disease-modifying therapies cannot be used. The PRAC further advised that patients being treated with Lemtrada who are benefitting from it may continue treatment in consultation with their doctor.[14]

Very common adverse reactions associated with alemtuzumab infusion in people with multiple sclerosis include upper respiratory tract and urinary tract infections, herpes virus infections, lymphopenia, leucopenia, changes in thyroid function, tachycardia, skin rashes, pruritus, pyrexia, and fatigue.[15] The Summary of Product Characteristics provided in the electronic Medicines Compendium [eMC [16]] further lists common and uncommon adverse reactions that have been reported for Lemtrada, which include serious opportunistic nocardial infections and cytomegalovirus syndrome.[17][18][19]

Alemtuzumab can also precipitate autoimmune disease through the suppression of regulatory T cell populations and/or the emergence of autoreactive B-cells.[20][21]

Cases of multiple sclerosis reactivation/relapse have also been reported[22]

Biochemical properties

[edit]

Alemtuzumab is a recombinant DNA-derived humanized IgG1 kappa monoclonal antibody that is directed against the cell surface glycoprotein CD52.[23]

History

[edit]

The origins of alemtuzumab date back to Campath-1 which was derived from the rat antibodies raised against human lymphocyte proteins by Herman Waldmann and colleagues in 1983.[24] The name Campath derives from the pathology department of Cambridge University.

Initially, Campath-1 was not ideal for therapy because patients could, in theory, react against the foreign rat protein determinants of the antibody. To circumvent this problem, Greg Winter and his colleagues humanised Campath-1, by extracting the hypervariable loops that had specificity for CD52 and grafting them onto a human antibody framework. This became known as Campath-1H and serves as the basis for alemtuzumab.[25]

While alemtuzumab started life as a laboratory tool for understanding the immune system, within a short time it was clinically investigated for use to improve the success of bone marrow transplants and as a treatment for leukaemia, lymphoma, vasculitis, organ transplants, rheumatoid arthritis and multiple sclerosis.[26]

Society and culture

[edit]

Economics

[edit]

Campath as a medication was first approved for B-cell chronic lymphocytic leukemia in 2001. It is marketed by Genzyme, which acquired the worldwide rights from Bayer AG in 2009. Genzyme was bought by Sanofi in 2011. In August/September 2012 Campath was withdrawn from the markets in the US and EU. This was done to prevent off-label use of the drug to treat multiple sclerosis and to prepare for a relaunch under the brand name Lemtrada, with a different dosage aimed at multiple sclerosis treatment, this is expected to be much higher-priced.[9]

In February 2011, Sanofi-Aventis, since renamed Sanofi, acquired Genzyme, the manufacturer of alemtuzumab.[27] The acquisition was delayed by a dispute between the two companies regarding the value of alemtuzumab.

In August 2012, Genzyme surrendered the license for all presentations of alemtuzumab,[28] pending regulatory approval to reintroduce it as a treatment for multiple sclerosis. Concerns[29] that Genzyme would later bring to market the same product at a much higher price proved correct.

Names

[edit]

Alemtuzumab is the international nonproprietary name.[30]

Research

[edit]

Antiviral properties

[edit]

In an in-vitro experiment, it has been shown that alemtuzumab has antiviral properties against HIV-1.[31]

Graft-versus-host disease

[edit]

A 2009 retrospective study of alemtuzumab (10 mg IV weekly) in 20 patients (no controls) with severe steroid-resistant acute intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT) demonstrated improvement. Overall response rate was 70%, with complete response in 35%.[32] In this study, the median survival was 280 days. Important complications following this treatment included cytomegalovirus reactivation, bacterial infection, and invasive aspergillosis infection.[32]

References

[edit]
  1. ^ "Alemtuzumab Use During Pregnancy". Drugs.com. 22 August 2022. Retrieved 6 January 2024.
  2. ^ "TGA eBS - Product and Consumer Medicine Information Licence".
  3. ^ "TGA eBS - Product and Consumer Medicine Information Licence".
  4. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  5. ^ "Campath- alemtuzumab injection". DailyMed. 3 May 2023. Retrieved 6 January 2024.
  6. ^ a b "Lemtrada- alemtuzumab injection, solution, concentrate". DailyMed. 23 May 2023. Retrieved 6 January 2024.
  7. ^ "Lemtrada EPAR". European Medicines Agency. 12 September 2013. Retrieved 6 January 2024.
  8. ^ a b c d e "Alemtuzumab Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 July 2019.
  9. ^ a b McKee S (21 August 2012). "Sanofi withdraws Campath in US and EU". Pharma Times Online. Pharma Times. Archived from the original on 4 March 2016. Retrieved 6 November 2012.
  10. ^ "About Campath". Genzyme. Archived from the original on 14 July 2011.
  11. ^ a b Zhang J, Shi S, Zhang Y, Luo J, Xiao Y, Meng L, et al. (November 2017). "Alemtuzumab versus interferon beta 1a for relapsing-remitting multiple sclerosis". The Cochrane Database of Systematic Reviews. 11 (11): CD010968. doi:10.1002/14651858.CD010968.pub2. PMC 6486233. PMID 29178444.
  12. ^ "FDA warns about rare but serious risks of stroke and blood vessel wall tears with multiple sclerosis drug Lemtrada (alemtuzumab)". FDA Drug Safety Communication. U.S. Food and Drug Administration (FDA). 29 November 2018.
  13. ^ Azevedo CJ, Kutz C, Dix A, Boster A, Sanossian N, Kaplan J (April 2019). "Intracerebral haemorrhage during alemtuzumab administration". The Lancet. Neurology. 18 (4): 329–331. doi:10.1016/S1474-4422(19)30076-6. PMID 30777657. S2CID 72334305.
  14. ^ "Use of multiple sclerosis medicine Lemtrada restricted while PRAC review is ongoing". Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC). European Medicines Agency. 12 April 2019.
  15. ^ "LEMTRADA 12 mg concentrate for solution for infusion - Summary of Product Characteristics (SMPC) - (Emc)". Archived from the original on 6 May 2021. Retrieved 7 April 2019.
  16. ^ "Home - electronic medicines compendium (emc)". www.medicines.org.uk. Retrieved 16 February 2024.
  17. ^ Sheikh-Taha M, Corman LC (May 2017). "Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis". Multiple Sclerosis. 23 (6): 872–874. doi:10.1177/1352458517694431. PMID 28290754. S2CID 206702778.
  18. ^ Clerico M, De Mercanti S, Artusi CA, Durelli L, Naismith RT (May 2017). "Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab". Multiple Sclerosis. 23 (6): 874–876. doi:10.1177/1352458516688350. PMID 28290755. S2CID 206702649.
  19. ^ Brownlee WJ, Chataway J (May 2017). "Opportunistic infections after alemtuzumab: New cases of norcardial infection and cytomegalovirus syndrome". Multiple Sclerosis. 23 (6): 876–877. doi:10.1177/1352458517693440. PMID 28290753. S2CID 30519152.
  20. ^ Costelloe L, Jones J, Coles A (March 2012). "Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis". Expert Review of Neurotherapeutics. 12 (3): 335–341. doi:10.1586/ern.12.5. PMID 22364332. S2CID 34738692.
  21. ^ Aranha AA, Amer S, Reda ES, Broadley SA, Davoren PM (2013). "Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review". Endocrine Practice. 19 (5): 821–828. doi:10.4158/EP13020.RA. PMID 23757618.
  22. ^ Wehrum T, Beume LA, Stich O, Mader I, Mäurer M, Czaplinski A, et al. (February 2018). "Activation of disease during therapy with alemtuzumab in 3 patients with multiple sclerosis". Neurology. 90 (7): e601–e605. doi:10.1212/WNL.0000000000004950. PMID 29352101. S2CID 3319939.
  23. ^ Klement A (7 January 2014). "Multiple-Sklerose-Behandlung". Österreichische Apothekerzeitung (in German) (1/2014): 24f.
  24. ^ Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, et al. (October 1983). "Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement". Blood. 62 (4): 873–882. doi:10.1182/blood.V62.4.873.873. PMID 6349718.
  25. ^ Riechmann L, Clark M, Waldmann H, Winter G (March 1988). "Reshaping human antibodies for therapy". Nature. 332 (6162): 323–327. Bibcode:1988Natur.332..323R. doi:10.1038/332323a0. PMID 3127726. S2CID 4335569.
  26. ^ "The life story of a biotechnology drug: Alemtuzumab". What is Biotechnology?.
  27. ^ Whalen J, Spencer M (17 February 2011). "Sanofi Buys Genzyme for over $20 billion". The Wall Street Journal.
  28. ^ Hussein J (9 August 2012). "Discontinuation of licensed supplies of alemtuzumab (Mabcampath)" (PDF). United Kingdom: National Institute for Health and Care Excellence.
  29. ^ "Multiple sclerosis: New drug 'most effective'". BBC News. 1 November 2012. Retrieved 1 November 2012.
  30. ^ World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90". WHO Drug Information. 37 (3). hdl:10665/373341.
  31. ^ Ruxrungtham K, Sirivichayakul S, Buranapraditkun S, Krause W (January 2016). "Alemtuzumab-induced elimination of HIV-1-infected immune cells". Journal of Virus Eradication. 2 (1): 12–18. doi:10.1016/S2055-6640(20)30694-4. PMC 4946689. PMID 27482429.
  32. ^ a b Schnitzler M, Hasskarl J, Egger M, Bertz H, Finke J (August 2009). "Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab". Biology of Blood and Marrow Transplantation. 15 (8): 910–918. doi:10.1016/j.bbmt.2009.04.002. PMID 19589480.
[edit]
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