Monday, 25 April 2016

Blinatumomab

Blinatumomab, AMG-103,  MEDI-538,  MT-103,
(Blincyto®) Approved
A bispecific CD19-directed CD3 T-cell engager used to treat philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Immunoglobulin, anti-​(human CD19 (antigen)​) (single-​chain) fusion protein with immunoglobulin, anti-​(human CD3 (antigen)​) (clone 1 single-​chain) (9CI)
 

Other Names

1: PN: WO2005052004 SEQID: 1 claimed protein

cas 853426-35-4
 
 BLINCYTO (blinatumomab) for injectionBlinatumomab (trade name Blincyto, previously known as AMG103) is a biopharmaceutical drug used as a second-line treatmentfor Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia. It belongs to a class of constructedmonoclonal 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.[1] 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.[2][3] When it launched, blinatumomab was priced at $178,000 per year in the United States; only about 1,000 people were eligible to take the drug, based on its label.[4]


Medical use

Blinatumomab is used as a second-line treatment for Philadelphia chromosome-negative relapsed or refractory Bcell precursor acute lymphoblastic leukemia.[2]

Mechanism of action


 
Blinatumomab linking a T cell to a malignant B cell.
Blinatumomab enables a patient's T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: aCD3 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.[5] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.[6]


History

The drug was developed by a German-American company Micromet, Inc. in cooperation with Lonza; Micromet was later purchased byAmgen, 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).[7] 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.[8]
On December 3, 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.[2][9]

Cost

When blinatumomab was approved, Amgen announced that the price for the drug would be $178,000 per year, which made it the most expensive cancer drug on the market. Merck's pembrolizumab was priced at $150,000 per year when it launched; unlike that drug and others, only about 1,000 people can be given the drug, based on its label.[4]
Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan-Kettering Cancer Center, has calculated that according to "value-based pricing," assuming that the value of a year of life is $120,000 with a 15% "toxicity discount," the market price of blinaumomab should be $12,612 a month, compared to the market price of $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.”[10]

 

Patent

WO 2010052013
Examples:
1. CD19xCD3 bispecific single chain antibody
The generation, expression and cytotoxic activity of the CD19xCD3 bispecific single chain antibody has been described in WO 99/54440. The corresponding amino and nucleic acid sequences of the CD19xCD3 bispecific single chain antibody are shown in SEQ ID NOs. 1 and 2, respectively. The VH and VL regions of the CD3 binding domain of the CD19xCD3 bispecific single chain antibody are shown in SEQ ID NOs. 7 to 10, respectively, whereas the VH and VL regions of the CD19 binding domain of the CD19xCD3 bispecific single chain antibody are shown in SEQ ID NOs 3 to 6, respectively.
PATENT
PATENT
WO 2015006749
PATENT
CN 104861067
WO1998008875A1 *18 Aug 19975 Mar 1998Viva Diagnostika Diagnostische Produkte GmbhNovel combination preparations and their use in immunodiagnosis and immunotherapy
WO1999054440A121 Apr 199928 Oct 1999Micromet Gesellschaft Für Biomedizinische Forschung MbhCD19xCD3 SPECIFIC POLYPEPTIDES AND USES THEREOF
WO2004106381A126 May 20049 Dec 2004Micromet AgPharmaceutical compositions comprising bispecific anti-cd3, anti-cd19 antibody constructs for the treatment of b-cell related disorders
WO2007068354A129 Nov 200621 Jun 2007Micromet AgMeans and methods for the treatment of tumorous diseases

References

  1.  "blinatumomab" (PDF). United States Adopted Names Council » Adopted Names.American Medical Association. 2008. N08/16.(registration required)
  2.  Blinatumomab label Updated 12/2014
  3.  Food and Drug Administration December 3, 2014 FDA Press release: Blinatumomab
  4.  Tracy Staton for FiercePharmaMarketing. December 18, 2014 Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto
  5.  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".Molecular Immunology 44 (8): 1935–43. doi:10.1016/j.molimm.2006.09.032.PMID 17083975.Closed access
  6.  Amgen (30 October 2012). Background Information for the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Meeting 04 December 2012 (PDF) (PDF). Food and Drug Administration. Blinatumomab (AMG 103).
  7.  "Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In Acute Lymphoblastic Leukemia" (Press release). Amgen. 1 July 2014.
  8.  "Amgen's BiTE® Immunotherapy Blinatumomab Receives FDA Priority Review Designation In Acute Lymphoblastic Leukemia" (Press release). Amgen. 9 October 2014.
  9. "Business: Antibody advance". Seven Days. Nature (paper) 516 (7530): 149. 11 December 2014. doi:10.1038/516148a.open access publication - free to read
  10.  Peter Loftus (June 18, 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.
Blinatumomab
Monoclonal antibody
TypeBi-specific T-cell engager
SourceMouse
TargetCD19, CD3
Clinical data
Trade namesBlincyto
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		intravenous
Legal status
Legal status
Pharmacokinetic data
Bioavailability100% (IV)
Metabolismdegradation into small peptides and amino acids
Biological half-life2.11 hours
Excretionurine (negligible)
Identifiers
CAS Number853426-35-4 
ATC codeL01XC19 (WHO)
ChemSpidernone
UNII4FR53SIF3A Yes
Chemical data
FormulaC2367H3577N649O772S19
Molar mass54.1 kDa
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