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| Drugs.com = {{drugs.com|monograph|ofatumumab}}
| Drugs.com = {{drugs.com|monograph|ofatumumab}}
| MedlinePlus = a610009
| MedlinePlus = a610009
| licence_EU = Arzerra
| licence_US = Ofatumumab
| licence_US = Ofatumumab
| pregnancy_US = C
| legal_UK = POM
| legal_US = Rx-only
| legal_US = Rx-only
| routes_of_administration = Intravenous, subcutaneous
| routes_of_administration = IV

<!--Pharmacokinetic data-->
| elimination_half-life = 14 days


<!--Identifiers-->
<!--Identifiers-->
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'''Ofatumumab'''<ref>{{cite journal|last=Zhang|first=Bodi|title=Ofatumumab|journal=MAbs|year=2009|volume=1|issue=4|pages=326–331|doi=10.4161/mabs.1.4.8895|url=http://www.landesbioscience.com/journals/17/article/8895/|pmid=20068404|pmc=2726602}}</ref> (trade name '''Arzerra''', also known as HuMax-CD20) is a [[human]] [[monoclonal antibody]] (for the [[CD20]] protein) which appears to inhibit early-stage B lymphocyte activation. It is FDA approved for treating [[chronic lymphocytic leukemia]] that is refractory to [[fludarabine]] and [[alemtuzumab]] (Campath) and has also shown potential in treating [[Follicular lymphoma|Follicular non-Hodgkin’s lymphoma]], [[Diffuse large B cell lymphoma]], [[rheumatoid arthritis]] and relapsing remitting [[multiple sclerosis]]. Ofatumumab has also received conditional approval in Europe for the treatment of refractory chronic lymphocytic leukemia. This makes ofatumumab the first marketing application for an antibody produced by [[Genmab]], as well as the first human monoclonal antibody which targets the CD20 molecule that will be available for patients with refractory CLL.
'''Ofatumumab'''<ref>{{cite journal|last=Zhang|first=Bodi|title=Ofatumumab|journal=MAbs|year=2009|volume=1|issue=4|pages=326–331|doi=10.4161/mabs.1.4.8895|url=http://www.landesbioscience.com/journals/17/article/8895/|pmid=20068404|pmc=2726602}}</ref> (trade name '''Arzerra''', also known as HuMax-CD20) is a [[human]] [[monoclonal antibody]] (for the [[CD20]] protein) which appears to inhibit early-stage B lymphocyte activation. It is FDA approved for treating [[chronic lymphocytic leukemia]] that is refractory to [[fludarabine]] and [[alemtuzumab]] (Campath) and has also shown potential in treating [[Follicular lymphoma|Follicular non-Hodgkin’s lymphoma]], [[Diffuse large B cell lymphoma]], [[rheumatoid arthritis]] and relapsing remitting [[multiple sclerosis]]. Ofatumumab has also received conditional approval in Europe for the treatment of refractory chronic lymphocytic leukemia. This makes ofatumumab the first marketing application for an antibody produced by [[Genmab]], as well as the first human monoclonal antibody which targets the CD20 molecule that will be available for patients with refractory CLL.


==Mechanism==
==Medical uses==
Its only indication that has received regulatory approval is [[Chronic lymphocytic leukaemia]] (CLL).<ref name = DM>{{cite web|title=ARZERRA (ofatumumab) injection, solution [GlaxoSmithKline LLC]|work=DailyMed|publisher=GlaxoSmithKline LLC|date=September 2013|accessdate=24 January 2014|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e6e738dc-9026-4cd3-8f85-7b10ac730e7d}}</ref><ref name = EMA>{{cite web|title=Arzerra : EPAR - Product Information|work=European Medicines Agency|publisher=Glaxo Group Ltd|date=7 March 2013|accessdate=24 January 2014|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001131/WC500093091.pdf|format=PDF}}</ref><ref name = EMC>{{cite web|title=Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)|work=electronic Medicines Compendium|publisher=GlaxoSmithKline UK|date=27 November 2013|accessdate=24 January 2014|url=http://www.medicines.org.uk/emc/medicine/23022/SPC/Arzerra+(acetate+formulation)/}}</ref> It first received FDA approval for this indication on the 26th of October 2009,<ref name = DM/> MHRA approval on the 19th of April 2010,<ref name = EMC/> EMA approval on the 14th of June 2010<ref name = EMA/> and [[Health Canada]] approval on the 13th of August 2012.<ref name = HC>{{cite web|title=Product Information|publisher=GlaxoSmithKline Inc.|work=Health Canada|date=13 August 2012|url=http://webprod5.hc-sc.gc.ca/dpd-bdpp/info.do?code=86740&lang=eng}}</ref>
Ofatumumab targets an [[epitope]] different from [[rituximab]] and most other CD20 directed antibodies. Ofatumumab binds to both the small and large loops of the CD20 molecule on B cells. Its location is in closer proximity to the membrane, which in theory allows for more effective complement deposition and subsequent B cell killing. The CD20 molecule is highly expressed in both normal and malignant B cells.


==Adverse effects==
==Approvals and indications==
'''<big>Adverse effects by frequency:</big>'''<ref name = DM/><ref name = EMA/><ref name = EMC/><br>
It was approved by FDA in Oct 2009 for [[chronic lymphocytic leukemia]] that is refractory to fludarabine and alemtuzumab.<ref>[http://www.hematology.org/News/2009/4384.aspx FDA Approves Ofatumumab (Arzerra) for Patients With CLL Refractory to Fludarabine and Alemtuzumab], October 2009</ref> It was conditionally approved by the EMA for refractory chronic lymphocytic leukemia in 2010. The results of the Phase III trail were announced in May 2013 and it was granted Breakthrough Therapy designation in combination with [[chlorambucil]] for the treatment of patients with chronic lymphocytic leukemia (CLL) who have not received prior treatment and are inappropriate for [[fludarabine]]-based therapy by the [[FDA]] in September 2013<ref>http://www.gsk.com/media/press-releases/2013/fda-grants-gsk-and-genmabs-arzerra---ofatumumab--breakthrough-th.html</ref>
'''Very common (>10% frequency):'''
{{colbegin|3}}
* Lower respiratory tract infection, including [[pneumonia]]
* Upper respiratory tract infection
* Rash
* [[Anaemia]]
* [[Neutropenia]]
{{colend}}

'''Common (1-10% frequency):''''
{{colbegin|5}}
* [[Sepsis]]
* Herpes virus infection
* [[Urinary tract infection]]
* Febrile neutropenia
* [[Leucopenia]]
* [[Thrombocytopenia]]
* Anaphylactoid reactions
* Hypersensitivity
* Tachycardia
* Hypotension
* Hypertension
* Bronchospasm
* Hypoxia
* Dyspnoea (shortness of breath)
* Chest discomfort
* Pharyngolaryngeal pain
* Cough
* Nasal congestion
* Small bowel obstruction
* Diarrhoea
* Nausea
* Urticaria (hives)
* Itchiness
* Flushing
* Back pain
* Cytokine release syndrome
* Pyrexia (fever)
* Rigors
* Chills
* Hyperhidrosis
* Fatigue
{{colend}}

'''Uncommon (0.1-1% frequency):'''
{{colbegin|4}}
* [[Agranulocytosis]]
* Coagulopathy
* Red cell aplasia
* [[Lymphopenia]]
* Anaphylactic shock
* [[Tumour lysis syndrome]]
{{colend}}

'''Rare (<0.1% frequency):'''
* [[Hepatitis B]] infection or reactivation

Ofatumumab has received a [[black box warning]] regarding the potential for it to cause [[progressive multifocal leukoencephalopathy]]and [[Hepatitis B]] reactivation.<ref name = MSR>{{cite web|title=Arzerra (ofatumumab) dosing, indications, interactions, and more|work=Medscape Reference|publisher=WebMD|accessdate=24 January 2014|url=http://reference.medscape.com/drug/arzerra-ofatumumab-999309#showall}}</ref> Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.<ref name = MSR/>

===Contraindications===
It is contraindicated in individuals that have hypersensitivity to ofatumumab or any of its excipients.<ref name = EMC/>

===Interactions===
No formal drug interaction studies have been conducted with ofatumumab.<ref name = DM/> Although it is advised that patients are not administered live virus vaccines (e.g. the oral polio vaccine) while undergoing treatment with ofatumumab due to the compromised ability to fight the attenuated viruses seen in patients being treated with ofatumumab.<ref name = MSR/>

==Mechanism==
Ofatumumab is a humanised anti-[[CD20]] monoclonal antibody whom's epitope is distinct from that of [[rituximab]].<ref name = Mech>{{cite journal|title=Ofatumumab: a novel monoclonal anti-CD20 antibody|journal=Pharmacogenomics and personalized medicine|date=2010|volume=3|pages=51-59|pmid=23226042|pmc=3513208|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513208/pdf/pgpm-3-051.pdf|format=PDF|author=Lin, TS}}</ref> The CD20 antigen is expressed on solely B cell lymphocytes.<ref name = Mech/> It binds more tightly to rituximab with a slower off-rate.<ref name = Mech/> It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC).<ref name = Mech/>


== Clinical trials ==
== Clinical trials ==
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* [[Rheumatoid arthritis]] (RA):
* [[Rheumatoid arthritis]] (RA):
** Phase III &ndash; OFA110635/GEN410 &ndash; Ofatumumab in adult RA patients who have had an inadequate response to [[methotrexate]]<ref>{{ClinicalTrialsGov|NCT00611455|Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to MTX Therapy}}</ref>
** Phase III &ndash; OFA110635/GEN410 &ndash; Ofatumumab in adult RA patients who have had an inadequate response to [[methotrexate]]<ref>{{ClinicalTrialsGov|NCT00611455|Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to MTX Therapy}}</ref>
** Phase III &ndash; OFA110634/GEN411 &ndash; Ofatumumab in adult RA patients who have had an inadequate response to [[TNF-alpha]] antagonist therapy<ref>{{ClinicalTrialsGov|NCT00603525|Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to TNF-α Antagonist Therapy}}</ref>
** Phase III &ndash; OFA110634/GEN411 &ndash; Ofatumumab in adult RA patients who have had an inadequate response to [[TNF-alpha]]antagonist therapy<ref>{{ClinicalTrialsGov|NCT00603525|Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to TNF-α Antagonist Therapy}}</ref>
* [[Diffuse large B cell lymphoma]] (DLBCL) &ndash; Phase III<ref>{{ClinicalTrialsGov|NCTNCT01014208|Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD}}</ref>
* [[Diffuse large B cell lymphoma]] (DLBCL) &ndash; Phase III<ref>{{ClinicalTrialsGov|NCTNCT01014208|Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD}}</ref>
* [[B-cell chronic lymphocytic leukemia]] (B-CLL) &ndash; Phase II<ref>{{ClinicalTrialsGov|NCT00349349|HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab}}</ref>
* [[B-cell chronic lymphocytic leukemia]] (B-CLL) &ndash; Phase II<ref>{{ClinicalTrialsGov|NCT00349349|HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab}}</ref>
Line 62: Line 135:
{{Reflist}}
{{Reflist}}


* {{cite journal |author=Coiffier B, Lepretre S, Pedersen LM, ''et al.'' |title=Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study |journal=Blood |volume=111 |issue=3 |pages=1094–100 |year=2008 |month=February |pmid=18003886 |doi=10.1182/blood-2007-09-111781 |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=18003886}}
* {{cite journal |author=Coiffier B, Lepretre S, Pedersen LM, ''et al.'' |title=Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study|journal=Blood |volume=111 |issue=3 |pages=1094–100 |year=2008 |month=February |pmid=18003886 |doi=10.1182/blood-2007-09-111781|url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=18003886}}
* {{cite journal |author=Zhang B |title=Ofatumumab |journal=MAbs |volume=1 |issue=4 |pages=326–31 |year=2009 |month=July |pmid=20068404 |pmc=2726602 |doi= 10.4161/mabs.1.4.8895|url=http://www.landesbioscience.com/journals/mabs/abstract.php?id=8895}}
* {{cite journal |author=Zhang B |title=Ofatumumab |journal=MAbs |volume=1 |issue=4 |pages=326–31 |year=2009 |month=July|pmid=20068404|pmc=2726602 |doi= 10.4161/mabs.1.4.8895|url=http://www.landesbioscience.com/journals/mabs/abstract.php?id=8895}}
* [http://clinicaltrials.gov/ct2/results?term=HuMax-CD20 ClinicalTrials.gov: HuMax-CD20 search results]
* [http://clinicaltrials.gov/ct2/results?term=HuMax-CD20 ClinicalTrials.gov: HuMax-CD20 search results]


Revision as of 04:48, 24 January 2014

Ofatumumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCD20
Clinical data
Trade namesArzerra
AHFS/Drugs.comMonograph
MedlinePlusa610009
License data
Routes of
administration		IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life14 days
Identifiers
CAS Number
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC6480H10022N1742O2020S44
Molar mass146.1 kDa g·mol−1
 ☒NcheckY (what is this?)  (verify)

Ofatumumab[2] (trade name Arzerra, also known as HuMax-CD20) is a human monoclonal antibody (for the CD20 protein) which appears to inhibit early-stage B lymphocyte activation. It is FDA approved for treating chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab (Campath) and has also shown potential in treating Follicular non-Hodgkin’s lymphoma, Diffuse large B cell lymphoma, rheumatoid arthritis and relapsing remitting multiple sclerosis. Ofatumumab has also received conditional approval in Europe for the treatment of refractory chronic lymphocytic leukemia. This makes ofatumumab the first marketing application for an antibody produced by Genmab, as well as the first human monoclonal antibody which targets the CD20 molecule that will be available for patients with refractory CLL.

Medical uses

Its only indication that has received regulatory approval is Chronic lymphocytic leukaemia (CLL).[3][4][5] It first received FDA approval for this indication on the 26th of October 2009,[3] MHRA approval on the 19th of April 2010,[5] EMA approval on the 14th of June 2010[4] and Health Canada approval on the 13th of August 2012.[6]

Adverse effects

Adverse effects by frequency:[3][4][5]
Very common (>10% frequency):

Common (1-10% frequency):'

  • Sepsis
  • Herpes virus infection
  • Urinary tract infection
  • Febrile neutropenia
  • Leucopenia
  • Thrombocytopenia
  • Anaphylactoid reactions
  • Hypersensitivity
  • Tachycardia
  • Hypotension
  • Hypertension
  • Bronchospasm
  • Hypoxia
  • Dyspnoea (shortness of breath)
  • Chest discomfort
  • Pharyngolaryngeal pain
  • Cough
  • Nasal congestion
  • Small bowel obstruction
  • Diarrhoea
  • Nausea
  • Urticaria (hives)
  • Itchiness
  • Flushing
  • Back pain
  • Cytokine release syndrome
  • Pyrexia (fever)
  • Rigors
  • Chills
  • Hyperhidrosis
  • Fatigue

Uncommon (0.1-1% frequency):

Rare (<0.1% frequency):

Ofatumumab has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathyand Hepatitis B reactivation.[7] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.[7]

Contraindications

It is contraindicated in individuals that have hypersensitivity to ofatumumab or any of its excipients.[5]

Interactions

No formal drug interaction studies have been conducted with ofatumumab.[3] Although it is advised that patients are not administered live virus vaccines (e.g. the oral polio vaccine) while undergoing treatment with ofatumumab due to the compromised ability to fight the attenuated viruses seen in patients being treated with ofatumumab.[7]

Mechanism

Ofatumumab is a humanised anti-CD20 monoclonal antibody whom's epitope is distinct from that of rituximab.[8] The CD20 antigen is expressed on solely B cell lymphocytes.[8] It binds more tightly to rituximab with a slower off-rate.[8] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC).[8]

Clinical trials

Status of clinical trials of ofatumumab conducted by Genmab and GSK, as of late 2010.

See also

References

  1. ^ "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 Oct 2023.
  2. ^ Zhang, Bodi (2009). "Ofatumumab". MAbs. 1 (4): 326–331. doi:10.4161/mabs.1.4.8895. PMC 2726602. PMID 20068404.
  3. ^ a b c d "ARZERRA (ofatumumab) injection, solution [GlaxoSmithKline LLC]". DailyMed. GlaxoSmithKline LLC. September 2013. Retrieved 24 January 2014.
  4. ^ a b c "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. Glaxo Group Ltd. 7 March 2013. Retrieved 24 January 2014.
  5. ^ a b c d "Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 27 November 2013. Retrieved 24 January 2014.
  6. ^ "Product Information". Health Canada. GlaxoSmithKline Inc. 13 August 2012.
  7. ^ a b c "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.
  8. ^ a b c d Lin, TS (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody" (PDF). Pharmacogenomics and personalized medicine. 3: 51–59. PMC 3513208. PMID 23226042.
  9. ^ http://clinicaltrials.gov/ct2/show/NCT00394836?term=nct00394836&rank=1
  10. ^ Clinical trial number NCT00611455 for "Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to MTX Therapy" at ClinicalTrials.gov
  11. ^ Clinical trial number NCT00603525 for "Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to TNF-α Antagonist Therapy" at ClinicalTrials.gov
  12. ^ Clinical trial number NCTNCT01014208 for "Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD" at ClinicalTrials.gov
  13. ^ Clinical trial number NCT00349349 for "HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab" at ClinicalTrials.gov
  14. ^ http://clinicaltrials.gov/ct2/show/NCT00811733?term=nct00811733&rank=1
  15. ^ http://clinicaltrials.gov/ct2/show/NCT00640328?term=nct00640328&rank=1
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