Blinatumomab

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Blinatumomab
Monoclonal antibody
Type Bi-specific T-cell engager
Source Mouse
Target CD19, CD3
Clinical data
Trade names Blincyto
Other namesAMG103, MT103
AHFS/Drugs.com Monograph
MedlinePlus a614061
License data
Pregnancy
category
Routes of
administration 		Intravenous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 100% (IV)
Metabolism degradation into small peptides and amino acids
Elimination half-life 2.11 hours
Excretion urine (negligible)
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C2367H3577N649O772S19
Molar mass 54086.56 g·mol−1
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Blinatumomab, sold under the brand name Blincyto, and known informally as blina, [4] is a biopharmaceutical medication 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. [5] 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. [6] [7]

Contents

Blinatumomab is given as a continuous IV infusion for 28 consecutive days per cycle. [6] 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. [6]

Medical use

Blinatumomab was originally approved to treat Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in adults and children. [8] 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. [6]

Mechanism of action

Blinatumomab linking a T cell to a malignant B cell. BiTE antibody en.svg
Blinatumomab linking a T cell to a malignant B cell.

Blinatumomab is a bispecific T-cell engager (BiTE). [6] 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. [9] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations. [10]

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). [11] 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. [12]

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. [6] [13]

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). [14] At the time of initial approval, only about 1,000 patients in the US had an indication for blinatumomab. [14]

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 blinatumomab 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." [15]

Related Research Articles

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References

  1. ↑ "Blinatumomab (Blincyto) Use During Pregnancy". Drugs.com. 29 May 2018. Retrieved 14 March 2020.
  2. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  3. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  4. ↑ "Exciting new cancer drug kinder than chemotherapy". BBC News. 17 January 2024. Retrieved 17 January 2024.
  5. ↑ "Blinatumomab" (PDF). United States Adopted Names Council » Adopted Names . American Medical Association. 2008. N08/16.(registration required)
  6. 1 2 3 4 5 6 "Blincyto- blinatumomab kit". DailyMed. 19 April 2019. Retrieved 14 March 2020.
  7. ↑ "Drug Approval Package: Blincyto (blinatumomab) Injection NDA #125557". U.S. Food and Drug Administration (FDA). 12 January 2015. Retrieved 14 March 2020.
  8. ↑ "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. Retrieved 26 October 2018.
  9. ↑ 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 logo transparent.svg
  10. ↑ 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.
  11. ↑ "Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE Antibody Blinatumomab In Acute Lymphoblastic Leukemia" (Press release). Amgen. 1 July 2014.
  12. ↑ "Amgen's BiTE Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia" (Press release). Amgen. 9 October 2014.
  13. ↑ 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.
  14. 1 2 Staton T (18 December 2014). "Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto". FiercePharmaMarketing.
  15. ↑ 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 . Retrieved 22 June 2015.
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