Blinatumomab

Blinatumomab
Monoclonal antibody
TypeBi-specific T-cell engager
SourceMouse
TargetCD19, CD3
Names
Trade namesBlincyto
Other namesAMG103, MT103
Clinical data
Drug classAntineoplastic agent
Main usesB-cell precursor acute lymphoblastic leukemia[1]
Side effectsInfection, fever, headache, infusion reactions, low red blood cells, low platelets, low white blood cells[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
    Routes of
    use    		Intravenous (IV)
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa614061
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability100% (IV)
    Metabolismdegradation into small peptides and amino acids
    Elimination half-life2.11 hours
    Excretionurine (negligible)
    Chemical and physical data
    FormulaC2367H3577N649O772S19
    Molar mass54086.56 g·mol−1

    Blinatumomab, sold under the brand name Blincyto, is a medication used to treat B-cell precursor acute lymphoblastic leukemia.[1] Specifically it is used for CD19-positive cases that have either failed other treatments or are in remission.[1] It is given by injection into a vein.[3]

    Common side effects include infection, fever, headache, infusion reactions, low red blood cells, low platelets, and low white blood cells.[1] Other side effects may include pancreatitis.[1] Use in pregnancy may harm the baby.[1] It is a monoclonal antibodies that binds to CD19 found on B cells and CD3 found on T cells, such that the later can kill the former.[4]

    Blinatumomab was approved for medical use in the United States in 2014 and Europe in 2015.[1][4] In the United Kingdom a vial of 38.5 micrograms costs the NHS about £2,020 as of 2021.[3] In the United States this amount costs about 4,500 USD.[5]

    Medical use

    Blinatumomab was originally approved to treat Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in adults and children.[6] It is approved by the US Food and Drug Administration (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.[1]

    Dosage

    Blinatumomab is given as a continuous IV infusion for 28 consecutive days per cycle involving a 24/7 infusion followed by a two week break from infusion.[1] The dose depends on a patient's actual body weight. Patients weighing over 45 kg should receive fixed doses while patients weighing less than 45 kg should receive doses based on their estimated body surface area.[1]

    Mechanism of action

    Blinatumomab linking a T cell to a malignant B cell.

    Blinatumomab is a bispecific T-cell engager (BiTE).[1] 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.[7] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.[8]

    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).[9] 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.[10]

    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.[1][11]

    Society and culture

    Cost

    When blinatumomab was approved, Amgen announced that the price for the drug would be US$178,000 per year, which made it the most expensive cancer drug on the market. Merck's pembrolizumab was priced at US$150,000 per year when it launched (in September 2014).[12] At the time of initial approval, only about 1,000 patients in the US had an indication for blinatumomab.[12]

    Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan-Kettering Cancer Center, calculated that according to "value-based pricing," assuming that the value of a year of life is US$121,000 with a 15% "toxicity discount," the market price of blinaumomab should be US$12,612 a month, compared to the market price of US$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."[13]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Blincyto- blinatumomab kit". DailyMed. 19 April 2019. Archived from the original on 28 October 2020. Retrieved 14 March 2020.
    2. ↑ "Blinatumomab (Blincyto) Use During Pregnancy". Drugs.com. 29 May 2018. Archived from the original on 4 December 2020. Retrieved 14 March 2020.
    3. 1 2 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 911. ISBN 978-0857114105.
    4. 1 2 "Blincyto". Archived from the original on 29 October 2021. Retrieved 11 January 2022.
    5. ↑ "Blincyto Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 22 March 2021. Retrieved 11 January 2022.
    6. ↑ "FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome-positive B cell" (Press release). U.S. Food and Drug Administration (FDA). 12 July 2017. Archived from the original on 22 December 2020. Retrieved 26 October 2018.
    7. ↑ Mølhøj M, Crommer S, Brischwein K, Rau D, Sriskandarajah M, Hoffmann P, et al. (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.closed access
    8. ↑ Amgen (30 October 2012). Background Information for the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Meeting 4 December 2012 (PDF) (Report). U.S. Food and Drug Administration (FDA). Blinatumomab (AMG 103). Archived from the original (PDF) on 9 May 2017. Retrieved 16 December 2019.
    9. ↑ "Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE Antibody Blinatumomab In Acute Lymphoblastic Leukemia" (Press release). Amgen. 1 July 2014. Archived from the original on 23 August 2015. Retrieved 13 March 2021.
    10. ↑ "Amgen's BiTE Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia" (Press release). Amgen. 9 October 2014. Archived from the original on 19 February 2015. Retrieved 13 March 2021.
    11. ↑ Jen EY, Xu Q, Schetter A, Przepiorka D, Shen YL, Roscoe D, et al. (January 2019). "FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease". Clinical Cancer Research. 25 (2): 473–477. doi:10.1158/1078-0432.CCR-18-2337. PMID 30254079.
    12. 1 2 Staton T (18 December 2014). "Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto". FiercePharmaMarketing. Archived from the original on 1 April 2016. Retrieved 13 March 2021.
    13. ↑ Loftus P (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. Archived from the original on 22 June 2015. Retrieved 22 June 2015.
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