Blinatumomab

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Blinatumomab
Mass / length primary structure 54.1 kDa
Identifier
External IDs
Drug information
Drug class Cancer immunotherapeutic

Blinatumomab (trade name Blincyto ; manufacturer Amgen ) is a bispecific antibody that is simultaneously directed against the CD3 receptor of T cells and against the surface protein CD19 of B cells . It is used as a biopharmaceutical drug in cancer medicine ( oncology ) for cancer immunotherapy for the treatment of special forms of acute lymphoblastic leukemia (ALL) . Blinatumomab is also the first so-called BiTE antibody used therapeutically .

Clinical information

Application areas (indications)

BLINCYTO is used to treat adults with the Philadelphia chromosome negative, relapsed, or refractory B-precursor acute lymphoblastic leukemia (ALL).

Type and duration of application

Treatment should be under the direction and supervision of a physician who is experienced in the management of haematological malignancies.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Bispecific binding of blinatumomab to a T cell and to a B cell tumor cell

Blinatumomab is a BiTE antibody and consists of two antigen- recognizing scFv fragments that are linked by a peptide bridge. One of the two scFv fragments binds specifically to the CD3 receptor of the T cells. The second scFv fragment is directed against the antigen CD19 , which is expressed on all B cells. In the case of a B-cell neoplasm, the tumor cells are thus recognized by CD19. By binding to the target proteins CD3 and CD19, these BiTE antibodies lead to a coupling of the malignant B cell to a T cell. The T cell is activated in this way and begins to produce and release cytotoxic proteins, such as the pore-forming protein perforin and granzyme , which trigger programmed cell death ( apoptosis ). As a result, the malignant B cell is destroyed. The T-cell-mediated recognition and destruction of malignant B-cells using BiTE antibodies is independent of the involvement of the major histocompatibility complex (MHC). Thus, a possible tumor resistance mechanism, the reduced expression of MHC proteins in tumor tissue, can be circumvented.

First results from clinical studies of phases I and II indicate that the experimental pharmacological properties can be transferred to an anti-tumor effect of blinatumomab in humans. This BiTE antibody showed an anti-tumor effect in acute lymphoblastic leukemia (ALL) in a phase II clinical study . A partial or complete tumor regression was also observed in the initial “proof-of-concept” study for the substance in patients with non-Hodgkin lymphoma .

Approval aspects

Admission status

Blincyto was approved in the EU in November 2015. It was approved in the USA in December 2014. Blinatumomab received the Breakthrough Therapy Designation from the US FDA and has been designated as an orphan drug in both the US and the EU .

Overall survival data

In June 2018, Amgen received approval from the European Registration Authority (EMA) to publish so-called Overall Survival Data relevant to registration . BLINCYTO is the first single-agent immunotherapy that has a superior overall survival advantage over standard therapy. For decades, overall survival has been the gold standard for assessing the effectiveness of blood cancer treatments.

Security aspects

This medicine is subject to additional monitoring. This enables new security knowledge to be identified quickly. Healthcare professionals are encouraged to report any suspected side effects. The pharmaceutical manufacturer Amgen has set up its own website to minimize risks (see web links).

history

Blinatumomab was originally developed by the German biotechnology company Micromet . Due to a takeover in 2012 by the biotechnology company Amgen , it entered Amgen's research pipeline. In July 2014, Amgen received the Breakthrough Therapy Designation for blinatumomab from the US FDA . In recognition of the current state of studies and the need for new drugs to treat ALL, a Breakthrough Therapy Designation u. a. an accelerated approval process. In October 2014, blinatumomab received the priority review designation . The drug approval for the treatment of relapsed or refractory B-precursor ALL by the FDA for the US market was granted in December 2014.

Web links

Individual evidence

  1. ↑ a b Baeuerle PA, Reinhardt C: Bispecific T-cell engaging antibodies for cancer therapy . In: Cancer Res . . 69, No. 12, June 2009, pp. 4941-4. doi : 10.1158 / 0008-5472.CAN-09-0547 . PMID 19509221 .
  2. ↑ Topp M, Goekbuget N, Kufer P, et al .: Treatment with anti-CD19 BiTE antibody blinatumomab (MT103 / MEDI-538) is able to eliminate minimal residual disease (MRD) in patients with B-precursor acute lmphoblastic leukemia (ALL ): First results of ongoing phase 2 study [ASH Annual Meeting Abstract] . In: Blood . 112, 2008, p. 1926.
  3. ↑ Topp MS, Kufer P, Gökbuget N, et al .: Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival . In: J Clin Oncol . . 29, 2011, p. 2493.
  4. ↑ Bargou R , Leo E, Zugmaier G, et al. : Tumor regression in cancer patients by very low doses of a T cell-engaging antibody . In: Science . 321, No. 5891, August 2008, pp. 974-7. doi : 10.1126 / science.1158545 . PMID 18703743 .
  5. ↑ a b European Commission Approves Amgen's BLINCYTO® (blinatumomab) for the Treatment of Adults with Philadelphia Chromosome-Negative Relapsed or Refractory B-precursor Acute Lymphoblastic Leukemia ( Memento of November 24, 2015 in the Internet Archive ), PM AMGEN of November 24, 2015 , accessed November 24, 2015.
  6. ↑ a b Blinatumomab , FDA notification dated December 3, 2014, accessed on November 24, 2015.
  7. ↑ FDA Approves BLINCYTO ™ (Blinatumomab) Immunotherapy for the Treatment of Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia , PM AMGEN, December 3, 2015, accessed November 24, 2015.
  8. ↑ Amgen Receives European Commission Approval To Add Overall Survival Data To BLINCYTO® (blinatumomab) Label ( Memento from June 27, 2018 in the Internet Archive ), PM Amgen from June 19, 2018, accessed on June 21, 2018.
  9. ↑ acquisition of Micromet by Amgen , PM by Amgen of 26 January 2012 called on July 2, 2014.
  10. ↑ Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In Acute Lymphoblastic Leukemia , Amgen PM July 1, 2014, accessed July 2, 2014.
  11. ↑ Amgen's BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia , Amgen PM, October 9, 2014, accessed October 10, 2014.
  12. ↑ US Food and Drug Administration: Blinatumomab . December 3, 2014. Retrieved February 23, 2015 ..