Sorafenib
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| Non-proprietary name | Sorafenib | |||||||||||||||||||||
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4- {4- [3- (4-chloro-3-trifluoromethylphenyl) ureido] phenoxy} pyridine-2-carboxylic acid methylamide ( IUPAC ) |
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| Molecular formula | C 21 H 16 ClF 3 N 4 O 3 | |||||||||||||||||||||
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| Molar mass | 464.83 g · mol -1 | |||||||||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||||||||
Sorafenib (trade name: Nexavar ® , manufacturer: Bayer AG ) is a protein kinase inhibitor from the group of multi-kinase inhibitors. He is in the form of tablets used and works by slowing the growth of cancer cells and the blood supply that fuels the cancer cells, inhibits.
Areas of application and approval
Sorafenib is an orphan drug and has been approved for a few indications in the EU since 2006. These were initially only the treatment of advanced kidney cancer when standard therapy has failed or is inappropriate, and the treatment of no more unresectable hepatocellular carcinoma (hepatocellular carcinoma, HCC). Since June 2014, sorafenib has also been approved in the EU for the treatment of metastatic differentiated thyroid carcinomas that no longer respond to radioiodine therapy .
A phase III study in the first-line treatment of advanced skin cancer was unsuccessful and was terminated prematurely. The clinical phase III study (indication of advanced lung cancer ) also failed to achieve the primary endpoint - an increase in overall survival.
pharmacology
As a multi-kinase inhibitor, sorafenib has several points of attack:
- It inhibits the Raf kinase and thus blocks the Raf signal cascade. Cell division and proliferation are reduced .
- It inhibits several other tyrosine kinases ; including those of the VEGF signal path. The signal cascades are blocked and tumor angiogenesis is reduced .
Side effects
The most common side effects are diarrhea, rash, hair loss , hand-foot syndrome , decreased number of lymphocytes ( lymphopenia ), bleeding (hemorrhage), high blood pressure ( arterial hypertension ), nausea, vomiting , reddening of the skin, itching , tiredness (exhaustion), pain as well increased amylase and lipase levels .
Compulsory license
The Indian patent office has granted the generics manufacturer Natco Pharma a compulsory license to produce Sorafenib Tosylate for the next eight years - against payment of a license fee of six percent of the sales proceeds. One of the reasons for this decision is that Bayer puts the monthly cost of this drug at almost 5,000 euros. With this patent transfer, the generics manufacturer can reduce costs to 175 US dollars, six percent of which is to be transferred to Bayer. This ruling is the first in the world to force a manufacturer to either lower their prices themselves or to leave the production to another company. However, Bayer has filed an objection to the compulsory licensing.
Compulsory licenses are anchored in international trade law and are listed in the Doha Declaration as a permissible exception to the TRIPS Agreement . They enable states to bypass existing patents in part in order to protect public health - for example, if patients' access to drugs is impaired by excessively high prices.
literature
Review article on pharmacology
- D. Strumberg: Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. In: Drugs Today . 41 (12), 2005 Dec, pp. 773-784. PMID 16474853 .
- DA Murphy, S. Makonnen, W. Lassoued, MD Feldman, C. Carter, WM Lee: Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006). In: Am J Pathol . 169 (5), 2006 Nov, pp. 1875-1885. PMID 17071608 , PMC 1780219 (free full text).
Review article on synthesis and analysis
- S. Afify, UR Rapp, P. Högger: Validation of a liquid chromatography assay for the quantification of the Raf kinase inhibitor BAY 43-9006 in small volumes of mouse serum. In: J Chromatogr B Analyt Technol Biomed Life Sci . 809 (1), 2004 Sep 25, pp. 99-103. PMID 15282098 .
- D. Bankston, J. Dumas, R. Natero, B. Riedl, KK Monahan, R. Silbey: A scaleable synthesis of BAY 43-9006: apotent Raf kinase inhibitor for the treatment of cancer. In: Organic Process Research & Development . 6 (6), 2002, pp. 777-781.
Web links
- European Public Assessment Report (EPAR) on Nexavar ( Memento of 22 August 2006 in the Internet Archive ) by the EMEA
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ Melanoma: study discontinued due to ineffectiveness of sorafenib. ( Memento from September 12, 2013 in the Internet Archive ) In: Deutsches Ärzteblatt. December 5, 2006.
- ↑ Nexavar® fails in lung cancer. In: Deutsche Apotheker Zeitung. May 22, 2012.
- ^ First compulsory license for a drug in India. on: aerzte-ohne-grenzen.at , March 12, 2012.
- ↑ Judgment of the Indian Patent Office (PDF; 2.2 MB) ( Memento of March 21, 2012 in the Internet Archive )
- ↑ Bayer is fighting for the Nexavar® patent. In: Deutsche Apotheker Zeitung. May 7, 2012.
