FDA Approves Blincyto (blinatumomab) for Precursor B-Cell Acute Lymphoblastic Leukemia
December 3, 2014 — The U.S. Food and Drug Administration today
approved Blincyto (blinatumomab) to treat patients with Philadelphia
chromosome-negative precursor B-cell acute lymphoblastic leukemia
(B-cell ALL), an uncommon form of ALL.
Blinatumomab (AMG103) is a drug that has anti-cancer properties. It belongs to a new 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.
The drug was developed by a German-American company Micromet, Inc. in cooperation with Lonza; Micromet was later purchases by Amgen, which has 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). In October 2014, Amgen’s Biologics License Application for blinatumomab was granted priority review designation by the FDA, thus establishing a deadline of May 19, 2015 for completion of the FDA review process.
Structure and mechanism of action
Blinatumomab enables a patient’s T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3site 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 andactivating the T cell to exert cytotoxic activity on the target cell. CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.
In a phase 1 clinical study with blinatumomab, patients with non-Hodgkin’s lymphoma showed tumor regression, and in some cases complete remission. There are ongoing phase 1 and phase 2 clinical trials of blinatumomab in patients with acute lymphoblastic leukemia (ALL). One phase II trial for ALL reported good results in 2010 and another is starting.
Common side effects observed in Phase 2 trials are listed below; they were temporary and typically occurred during the first treatment cycle:
- Flu-like symptoms (i.e. fever, headache, and fatigue)
- Weight increase
- Decrease of blood immunoglobulin
CNS effects were also observed during clinical trials and were treated via a lower dose of blinatumomab, administration of dexamethasone, or treatment discontinuation. Because the side effects were reversible, early monitoring for the CNS symptoms listed below is important:
- Speech disorders
- Statement on a Nonproprietary Name adopted by the USAN Council: Blinatumomab
- Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In Acute Lymphoblastic Leukemia
- Amgen’s BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia
- 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”. Mol Immunol 44 (8): 1935–43. doi:10.1016/j.molimm.2006.09.032. PMID 17083975.
- Background Information for the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Meeting 04 December 2012
- Bargou, R; et al. (2008). “Tumor regression in cancer patients by very low doses of a T cell-engaging antibody”. Science 321 (5891): 974–977. doi:10.1126/science.1158545.PMID 18703743.
- ClinicalTrials.gov NCT00560794 Phase II Study of the BiTE Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute ALL
- “Micromet initiates MT103 phase 2 trial in adult ALL patients”. 20 Sep 2010.
|Type||Bi-specific T-cell engager|
|Mol. mass||54.1 kDa|