Blinatumomab

Blinatumomab (trade name Blincyto) is a biopharmaceutical drug used as a second-line treatment for Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia. It belongs to a class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells.[1] In December 2014, it was approved by the US Food and Drug Administration under the accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at the time of approval.[2][3]

Blinatumomab
Monoclonal antibody
TypeBi-specific T-cell engager
SourceMouse
TargetCD19, CD3
Clinical data
Trade namesBlincyto
Other namesAMG103, MT103
AHFS/Drugs.comMonograph
MedlinePlusa614061
License data
Pregnancy
category
  • AU: C
  • US: N (Not classified yet)
    Routes of
    administration    		intravenous
    Drug classAntineoplastic agent
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability100% (IV)
    Metabolismdegradation into small peptides and amino acids
    Elimination half-life2.11 hours
    Excretionurine (negligible)
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    KEGG
    Chemical and physical data
    FormulaC2367H3577N649O772S19
    Molar mass54.1 kg/mol g·mol−1
     NY (what is this?)  (verify)

    Blinatumomab is given as a continuous IV infusion for 28 consecutive days per cycle.[2] The dose depends on a patient's actual body weight. Patients weighing over 45kg should receive fixed doses while patients weighing less than 45kg should receive doses based on their estimated body surface area. [2]

    Medical use

    Blinatumomab was originally approved to treat Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in adults and children.[4] It is currently approved by the US FDA for B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease greater than or equal to 0.1% as well as relapsed or refractory B-cell precursor ALL. [2]

    Mechanism of action
    Blinatumomab linking a T cell to a malignant B cell.

    Blinatumomab is a bispecific T-cell engager (BiTE).[2] It enables a patient's T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.[5] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.[6]

    History

    The drug (originally known as MT103) was developed by a German-American company Micromet, Inc. in cooperation with Lonza; In 2012, Micromet was purchased by Amgen, which furthered the drug's clinical trials.

    In July 2014, the FDA granted breakthrough therapy status to blinatumomab for the treatment of acute lymphoblastic leukemia (ALL).[7] In October 2014, Amgen's Biologics License Application for blinatumomab was granted priority review designation by the FDA, thus establishing a deadline of 19 May 2015, for completion of the FDA review process.[8]

    On 3 December 2014, the drug was approved for use in the United States to treat Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia under the FDA's accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at the time of approval.[2][9]

    Cost

    When blinatumomab was approved, Amgen announced that the price for the drug would be $178,000 per year, which made it the most expensive cancer drug on the market. Merck's pembrolizumab was priced at $150,000 per year when it launched (in Sept 2014).[10] At the time of initial approval, only about 1,000 patients in the US had an indication for blinatumomab. [10]

    Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan-Kettering Cancer Center, has calculated that according to "value-based pricing," assuming that the value of a year of life is $121,000 with a 15% "toxicity discount," the market price of blinaumomab should be $12,612 a month, compared to the market price of $64,260 a month. A representative of Amgen said, "The price of Blincyto reflects the significant clinical, economic and humanistic value of the product to patients and the health-care system. The price also reflects the complexity of developing, manufacturing and reliably supplying innovative biologic medicines."[11]

    References
    1. "blinatumomab" (PDF). United States Adopted Names Council » Adopted Names. American Medical Association. 2008. N08/16.(registration required)
    2. Blinatumomab label Updated 5/2018.
    3. Food and Drug Administration 3 December 2014 FDA Press release: Blinatumomab
    4. Research, Center for Drug Evaluation and. "Approved Drugs - FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome-positive B cell". www.fda.gov. Retrieved 26 October 2018.
    5. Mølhøj, M; Crommer, S; Brischwein, K; Rau, D; Sriskandarajah, M; Hoffmann, P; Kufer, P; Hofmeister, R; Baeuerle, PA (March 2007). "CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis". Molecular Immunology. 44 (8): 1935–43. doi:10.1016/j.molimm.2006.09.032. PMID 17083975.
    6. Amgen (30 October 2012). Background Information for the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Meeting 4 December 2012 (PDF) (PDF). Food and Drug Administration. Blinatumomab (AMG 103).
    7. "Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In Acute Lymphoblastic Leukemia" (Press release). Amgen. 1 July 2014.
    8. "Amgen's BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia" (Press release). Amgen. 9 October 2014.
    9. "Business: Antibody advance". Seven Days. Nature (paper). 516 (7530): 149. 11 December 2014. doi:10.1038/516148a.
    10. Tracy Staton for FiercePharmaMarketing. 18 December 2014 Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto
    11. Peter Loftus (18 June 2015). "How Much Should Cancer Drugs Cost? Memorial Sloan Kettering doctors create pricing calculator that weighs factors such as side effects, extra years of life". The Wall Street Journal. Retrieved 22 June 2015.
    • "Blinatumomab". Drug Information Portal. U.S. National Library of Medicine.
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