Ofatumumab

Ofatumumab
Mass / length primary structure	146  kDa
Identifier
External IDs	CAS number : 679818-59-8
Drug information
ATC code	L01 XC10
Drug class	Cytostatic , monoclonal antibody

Fab fragment (fragment of antigen binding) from ofatumumab

Ofatumumab ( Arzerra, HuMax-CD20 ) is a human monoclonal antibody (IgG1) that has been used in the treatment of certain types of leukemia .

Mode of action

Ofatumumab binds specifically to the CD20 protein on the B lymphocytes , to a specific epitope that includes both extracellular loops, the small and the large, of the CD20 molecule. This triggers cytotoxicity, which leads to lysis of the cells. Ofatumumab also works on cells that are resistant to rituximab .

application

Ofatumumab has been used in patients with chronic lymphocytic leukemia who are refractory to fludarabine and alemtuzumab . The approval, which is based on the interim result of a single-arm, multi-center phase III study, was granted on the condition that further study data would be submitted later. Ofatumumab monotherapy resulted in a response rate of 58% in double refractory patients in the pivotal study. Ofatumumab has been studied for use in other types of cancer, such as: B. follicular non-Hodgkin lymphoma and diffuse large B-cell lymphoma .

dosage

The normal infusion schedule consisted of 8 consecutive weekly infusions with 300 mg of ofatumumab on the 1st and 2000 mg on the following infusions. This was followed by 4 more infusions at monthly intervals. In addition, a prednisone equivalent as well as an analgesic and an antihistamine were administered.

Side effects

In the registration study (Hx-CD20-406), in addition to infusion reactions such as fever, chills and cardiac events, bacterial, viral and fungal infections frequently occurred. Common side effects are also neutropenia , thrombocytopenia , leukopenia , tachycardia , nausea, pain in the nasopharynx and back.

After the occurrence of fulminant hepatitis during therapy with ofatumumab, a red hand letter was published on December 16, 2013 . Hepatitis B virus (HBV) screening is recommended before starting treatment. Patients with active hepatitis B should not be treated with the antibody. In the case of a positive hepatitis B serology , possible use must be monitored and, if necessary, accompanied by antiviral therapy.

Admission status

The drug was approved by the European Medicines Agency (EMA) , resp. approved by the European Commission in April 2010. Approval by the US Food and Drug Administration (FDA) was granted in April 2014. In May 2014, the CHMP gave a positive vote in favor of an extension of the approval in Europe. On February 28, 2019, Novartis withdrew the drug from the market and withdrew its approval. The reason for this was the very low demand, now that alternative drug treatment methods exist.

Treatment of Multiple Sclerosis

Novartis is developing a drug ofatumumab to treat multiple sclerosis . In two studies, the drug reached the primary endpoint under the name Asclepios . The agent was administered subcutaneously once a month. Compared to teriflunomide , there is a better relapse rate and a longer period before an increase in disability occurs. The application for approval could still be submitted in 2019.

See also

• Monoclonal Antibody Nomenclature : Convention for naming monoclonal antibodies

literature

• ABDA database via WINAPO Lauer Taxe: data sheet for Arzerra, as of May 15, 2011
• Pharmaceutical newspaper , as of May 17, 2011

Web links

• Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Ofatumumab

Individual evidence

1. ↑ Drug Safety Mail 2013-66 - Rote-Hand-Brief on Arzerra® (ofatumumab): Hepatitis B virus (HBV) screening before the start of treatment . ( Memento from December 20, 2013 in the Internet Archive ) Medicines Commission of the German Medical Association, December 16, 2013.
2. ↑ Arzerra-ofatumumab , European public assessment report (EPAR), accessed on April 21, 2014
3. ↑ GSK and Genmab receive FDA approval for Arzerra® (ofatumumab) as first-line treatment in combination with chlorambucil for patients with Chronic Lymphocytic Leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate . ( Memento of April 22, 2014 in the Internet Archive ) PM by GSK, April 17, 2014; Retrieved April 21, 2014
4. ↑ GSK and Genmab receive CHMP positive opinion for Arzerra (ofatumumab) in combination with chlorambucil or bendamustine as a first-line treatment for patients with chronic lymphocytic leukaemia (CLL) who are not eligible for fludarabine-based therapy . ( Memento of May 25, 2014 in the Internet Archive ) Press release by GSK, May 23, 2014; Retrieved May 25, 2014
5. ↑ DeutschesArztPortal - recall of March 4, 2019 , accessed on September 21, 2019
6. ↑ Novartis leaves competition in the shadows with multiple sclerosis drugs on cash.ch, accessed on September 21, 2019
7. ↑ Stephen L. Hauser, Amit Bar-Or, Jeffrey A. Cohen, Giancarlo Comi, Jorge Correale: Ofatumumab versus Teriflunomide in Multiple Sclerosis . In: New England Journal of Medicine . tape 383 , no. 6 , August 6, 2020, ISSN  0028-4793 , p. 546–557 , doi : 10.1056 / NEJMoa1917246 ( nejm.org [accessed August 20, 2020]).
8. ↑ Ofatumumab achieves study endpoints on amsel.de, accessed on September 21, 2019

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