Talk:Ofatumumab

Ofatumumab page updates for Talk submission

My name is Laura Henao and I am an employee of Novartis, being paid by Novartis. We noticed that some of the information on the Ofatumumab Wikipedia page (http://en.wiki.x.io/wiki/Ofatumumab) is outdated.

We wanted to share some suggestions of updates (see below), with information that can be verifiably sourced at the links included for every suggested change. The changes are made on behalf of Novartis.

Please find below the rationale behind these suggested updates:

1. Presenting Kesimpta first in the introduction: People who are searching for ofatumumab are more likely to search information on Kesimpta, as it is a treatment available in more regions than Arzerra and indicated for the treatment of relapsing forms of multiple sclerosis, a disease with higher prevalence.

2. Adding missing information on both Kesimpta and Arzerra: The treatments are not clearly differentiated on the current version, which makes it difficult to understand what information applies to which treatment (e.g., routes of administration, approvals, adverse effects, etc.).

3. Simplifying the history section: It is currently dense and complex to follow, and contains unsourced information.

Please let me know at your earliest convenience if these edits are approved and any next steps to update the article. I appreciate your time and consideration.

Changes info box on the right-hand side:

Clinical data

MedlinePlus: add a621060 and link to https://medlineplus.gov/druginfo/meds/a621050.html.  

Routes of administration: after ‘Intravenous’, add ‘(Arzerra) and after ‘subcutaneous’, add ‘(Kesimpta)’

ATC code: Add Arzerra and Kesimpta after ‘L01FA02’, add ‘(Arzerra)’, and after ‘L04AA52’, add ‘(Kesimpta)’

Identifiers: update the link for CAS Number to: https://www.chemblink.com/products/679818-59-8.htm - the current link is broken

Introduction:

Change “Ofatumumab is a fully human monoclonal antibody to CD20, which inhibit early-stage B lymphocyte activation. Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States.[6]” to “Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion.” (Add reference: Hauser SL, Bar-Or A, Cohen JA, et al; for the ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis [supplemental appendix]. N Engl J Med.)

Switch the order to name Kesimpta first here: Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the EU and other regions.[7][9] Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States.[6]

Again, switch the order to name Kesimpta first here: The most common side effects for ofatumumab (Kesimpta) include upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions. The most common side effects for ofatumumab (Arzerra) include infusion reactions and neutropenia.”

Medical uses:

Delete “Ofatumumab is indicated for the treatment of untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL).[6][8][10][4] In the United States and the European Union it is also indicated for the treatment of relapsing forms of multiple sclerosis in adults.[7][9][11]”

Add “Ofatumumab (Kesimpta 20 mg solution for injection in pre-filled syringe/pen) is indicated for the treatment of relapsing forms of multiple sclerosis in adults.[7][9][12] The recommended dose is 20 mg of ofatumumab administered by subcutaneous injection with monthly dosing following loading (add references: https://www.ema.europa.eu/en/documents/product-information/kesimpta-epar-product-information_en.pdf and https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125326s070lbl.pdf). Treatment with ofatumumab has been shown to rapidly deplete B-cells (add references: https://www.ema.europa.eu/en/documents/product-information/kesimpta-epar-product-information_en.pdf and https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125326s070lbl.pdf), which aids MS pathogenesis by influencing and regulating different autoimmune process such as T-cell production and APC activity. (Add reference: Arneth, B. Impact of B cells to the pathophysiology of multiple sclerosis. J Neuroinflammation 16, 128 (2019).) Depleted B-cells are required to address chronic clinical conditions like MS. Ofatumumab (Arzerra 100 mg or 1000 mg concentrate for solution for infusion) is indicated for the treatment of untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL).[6][8][11][4] The recommended doses for treatment of CLL are higher than MS, with 1000 or 2000 mg infusions administered monthly depending on if the CLL is untreated, relapsed or refractory, following loading.” (Add reference: "Arzerra (ofatumumab) Information". U.S. Food and Drug Administration. 3 November 2018. Retrieved 11 September 2021.)

Change “It is under investigation as a potential treatment for follicular lymphoma, diffuse large B cell lymphoma and rheumatoid arthritis.[citation needed]” to “Ofatumumab is under investigation as a potential treatment for follicular lymphoma, diffuse large B cell lymphoma and rheumatoid arthritis.[citation needed]”

Adverse effects:

Add “Adverse effects of ofatumumab (Kesimpta) by frequency:” (add references: https://www.ema.europa.eu/en/documents/product-information/kesimpta-epar-product-information_en.pdf and https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125326s070lbl.pdf) above “Adverse effects by frequency:[6][10][4]”

Add “Very common (<10% frequency):

Upper respiratory tract infection

Injection-related reactions (systemic)

Injection-site reactions (local)

Urinary tract infections

Headache

Add “Common (1-10% frequency)”:

Back pain

Blood immunoglobulin M decreased

Oral herpes”

Change “Adverse effects by frequency [6][10][4]” to “Adverse effects of ofatumumab (Arzerra) by frequency:[6][10][4]”

Add the following to the list of “Very common (>10% frequency)” adverse effects for Arzerra:

Dyspnea

Cough

Nausea

Diarrhea

Pyrexia

Fatigue

Bronchitis

Add the following to the list of “Common (1-10% frequency)” adverse effects for Arzerra:

Infusion reaction

Cytopenia

Headache”

Delete the following to the list of “Common (1-10% frequency)” adverse effects for Arzerra:

Dyspnea (shortness of breath)

Cough

Diarrhea

Nausea

Urticaria (hives)

Pyrexia (fever)

Fatigue

Add the following to the list of “Uncommon (0.1-1% frequency)” adverse effects for Arzerra:

Hepatitis B infection and reactivation

Bradycardia

Replace “Anaphylactic shock” with “Anaphylactic reactions” in the list of “Uncommon (0.1-1% frequency)” adverse effects for Arzerra

In the final paragraph, change “Ofatumumab has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathy and hepatitis B reactivation.[12][13]” to “Ofatumumab (Arzerra) has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathy and hepatitis B reactivation.[12][13]”

Add the sentence “For more information, please refer to the prescribing information or your doctor.” at the end of this section

Interactions:

Add sentence “While on treatment with ofatumumab (Kesimpta), all immunizations should be administered according to immunization guidelines at least 4 weeks prior to initiation of ofatumumab for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ofatumumab for inactivated vaccines.” to the end of the existing paragraph (add reference: https://www.ema.europa.eu/en/documents/product-information/kesimpta-epar-product-information_en.pdf)

Mechanism:

Change “Ofatumumab is a human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[14]” to “Ofatumumab is a fully human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[14]”

Add sentence “Ofatumumab binds to a distinct epitope on small and large extracellular loops of CD20.” to paragraph after first sentence, “Ofatumumab is a fully human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[14]” (Add references: Teeling JL, et al. J Immunol. 2006;177:362–371 and Smith P, et al. ECTRIMS 2016. P.1143)

History:

Change “Ofatumumab was developed by GlaxoSmithKline GSK plc. As Arzerra it was approved for medical use in the United States in October 2009.[15][16]” to “Ofatumumab was jointly developed by Danish biotech Genmab and GlaxoSmithKline GSK plc who entered into an agreement to co-develop and commercialize ofatumumab in 2006 (add reference: https://ir.genmab.com/static-files/0ed47252-19fa-4599-b9d8-0c5b6389aff5.) It was approved as Arzerra for the treatment of chronic lymphocytic leukemia in the United States in October 2009.[15][16]”

Change “Ofatumumab (Arzerra) was approved for medical use in the European Union in June 2010,[10][4] and for use in Canada in August 2012.[17][18] It was approved for use in the UK in April 2010.[4]” to “Ofatumumab (Arzerra) was then approved in the European Union in June 2010,[10], in the UK in April 2010 [4] and in Canada in August 2012.[17][18]”

Add sentence “In 2014 Novartis acquired a number of GSK’s oncology products, including the collaboration with Genmab and ofatumumab.” after “Ofatumumab (Arzerra) was then approved in the European Union in June 2010,[10], in the UK in April 2010 [4] and in Canada in August 2012.[17][18]”. (Add references: https://www.bioprocessonline.com/doc/genmab-to-transfer-ofatumumab-from-gsk-to-novartis-0001 and https://www.gsk.com/en-gb/media/press-releases/gsk-completes-divestment-of-rights-to-ofatumumab-for-auto-immune-indications-to-novartis/).

Delete “As part of the product-swap between GSK plc and Novartis the compound came to Novartis, but the rights for use in Multiple Sclerosis were excluded from the deal. Though a new contract was necessary and delayed the development for Multiple Sclerosis.”

Change “For commercial reasons, to develop Ofatumumab for the use in Multiple Sclerosis, a new brand needed to be created. Though Ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017.[17][18]” to “For commercial reasons, Ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017.[17][18]”

Change “Ofatumumab (Kesimpta) was approved for medical use in the United States in August 2020.[11][23]” to “Ofatumumab (Kesimpta) was approved for the treatment of relapsing forms of multiple sclerosis in adults in the United States in August 2020.[11][23]”

Delete “On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kesimpta, intended for the treatment of adults with active relapsing forms of multiple sclerosis.[24] The applicant for this medicinal product is Novartis Ireland Limited.[24]”

Change “Ofatumumab (Kesimpta) was approved for medical use in the European Union.[9] to “EU approval was subsequently received in March 2021.[9]” NVSEDITOR (talk) 15:31, 26 September 2022 (UTC)

Changes for the Ofatumumab Wikipedia page

Hello,

Following up on the suggested changes for the Ofatumumab Wikipedia page (http://en.wiki.x.io/wiki/Ofatumumab) in my previous message, I plan to make these changes to the page in two weeks, unless there are any objections or questions from the community?

Please let me know if these edits are approved. I appreciate your time and consideration.

Kind regards,

Laura Henao NVSEDITOR (talk) 09:57, 10 October 2022 (UTC)