Blinatumomab Explained

Blinatumomab, sold under the brand name Blincyto, and known informally as blina,[1] 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.[2] 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.[3] [4] Blinatumomab is given via intravenous infusion.

Medical use

Blinatumomab was originally approved to treat Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in adults and children.[5] 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.

Mechanism of action

Blinatumomab is a bispecific T-cell engager (BiTE). 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.[6] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.[7]

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).[8] 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.[9]

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.[3] [10]

Cost

When blinatumomab was approved, Amgen announced that the price for the drug would be per year, which made it the most expensive cancer drug on the market. Merck's pembrolizumab was priced at per year when it launched (in September 2014). At the time of initial approval, only about 1,000 patients in the US had an indication for blinatumomab.[11]

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 with a 15% "toxicity discount," the market price of blinatumomab should be a month, compared to the market price of 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."[12]

Notes and References

  1. News: 2024-01-17 . Exciting new cancer drug kinder than chemotherapy . 2024-01-17 . BBC News . en-GB.
  2. Web site: Blinatumomab . . 2008 . N08/16 . .
  3. Web site: Blincyto- blinatumomab kit . DailyMed . 19 April 2019 . 14 March 2020.
  4. Web site: Drug Approval Package: Blincyto (blinatumomab) Injection NDA #125557 . U.S. Food and Drug Administration (FDA) . 12 January 2015 . 14 March 2020.
  5. FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome-positive B cell . U.S. Food and Drug Administration (FDA) . 12 July 2017 . 2018-10-26.
  6. Mølhøj M, Crommer S, Brischwein K, Rau D, Sriskandarajah M, Hoffmann P, Kufer P, Hofmeister R, Baeuerle PA . 6 . 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 . March 2007 . 17083975 . 10.1016/j.molimm.2006.09.032 .
  7. Background Information for the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Meeting 4 December 2012 . 30 October 2012 . Amgen . Amgen . U.S. Food and Drug Administration (FDA) . Blinatumomab (AMG 103) . 16 December 2019 . https://web.archive.org/web/20170509210243/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM330210.pdf . 9 May 2017 . dead .
  8. Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE Antibody Blinatumomab In Acute Lymphoblastic Leukemia . 1 July 2014 . .
  9. Amgen's BiTE Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia . . 9 October 2014 .
  10. Jen EY, Xu Q, Schetter A, Przepiorka D, Shen YL, Roscoe D, Sridhara R, Deisseroth A, Philip R, Farrell AT, Pazdur R . 6 . 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 . January 2019 . 30254079 . 10.1158/1078-0432.CCR-18-2337 . free .
  11. Web site: Tracy . Staton . vanc . FiercePharmaMarketing . 18 December 2014 . Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto .
  12. News: Peter . Loftus . vanc . How Much Should Cancer Drugs Cost? Memorial Sloan Kettering doctors create pricing calculator that weighs factors such as side effects, extra years of life . 22 June 2015 . . 18 June 2015 . subscription .