Obinutuzumab

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Obinutuzumab?
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target CD20
Clinical data
Trade names Gazyva, Gazyvaro
Legal status
Routes of
administration
Intravenous infusion
Pharmacokinetic data
Biological half-life 28.4 days
Identifiers
CAS Registry Number 949142-50-1 N
ATC code L01XC15
UNII O43472U9X8 YesY
KEGG D09321 YesY
Chemical data
Formula C6512H10060N1712O2020S44
Molecular mass 146.1 kDa
 N (what is this?)  (verify)

Obinutuzumab (called afutuzumab until 2009[1]) is a humanized monoclonal antibody, originated by GlycArt Biotechnology AG and developed by Biogen Idec, Chugai Pharmaceutical Co., and Hoffmann-La Roche Inc. for the treatment of lymphoma.[2] It acts as an immunomodulator.[3][4]

Obinutuzumab targets CD20 and kills B cells.[2] GlycArt's technology platform allowed control of protein glycosylation; the cells in which obinutuzumab is produced were engineered to overexpress two glycosylation enzymes, MGAT3 and Golgi mannosidase 2, which reduce the amount of fucose attached to the antibody, which in turn increases the antibody's ability to activate natural killer cells.[5][6]

Obinutuzumab was approved under the trade name Gazyva by the US FDA in 2013, and as Gazyvaro by the EMA in Europe, for the treatment of chronic lymphocytic leukemia in combination with chemotherapy in treatment-naive patients. Patients treated with Gazyva had median survival of 23 months before death or disease progression, compared with 11.1 months for patients on chemotherapy alone.[7]

UK availability[edit]

In October 2014, NICE announced that NHS England would not fund use of the drug, due to data uncertainties in Roche's application.[8]

Breakthrough therapy designation[edit]

Main article: Breakthrough therapy

On November 13, 2013 the United States Food and Drug Administration approved Gazyva for chronic lymphocytic leukemia making it the first drug to receive the coveted breakthrough therapy designation[9]

References[edit]

  1. ^ International Nonproprietary Names for Pharmaceutical Substances (INN), World Health Organization.
  2. ^ a b Robak, T (2009). "GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies" (PDF). Current opinion in investigational drugs (London, England : 2000) 10 (6): 588–96. PMID 19513948. 
  3. ^ Statement On A Nonproprietary Name Adopted By The Usan Council - Afutuzumab, American Medical Association.
  4. ^ International Nonproprietary Names for Pharmaceutical Substances (INN), World Health Organization.
  5. ^ Ratner M. Genentech's glyco-engineered antibody to succeed Rituxan. Nat Biotechnol. 2014 Jan;32(1):6-7. PMID 24406911
  6. ^ Umaña P et al. Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat Biotechnol. 1999 Feb;17(2):176-80. PMID 10052355
  7. ^ Associated Press, published in the New York Times. November 1, 2013 F.D.A. Clears New Cancer-Fighting Drug From Roche
  8. ^ "NICE denies Roche cancer drug due to ‘data uncertainties’". PM Live. Retrieved 3 October 2014. 
  9. ^ FDA approves Gazyva for chronic lymphocytic leukemia: Drug is first with breakthrough therapy designation to receive FDA approval, FDA NEWS RELEASE, FDA, November 13, 2013, retrieved July 20, 2015