Collagenase clostridium histolyticum
|Pregnancy cat.||B (US)|
|Legal status||℞ Prescription only|
|Mol. mass||114 kDa (AUX-I),
113 kDa (AUX-II)
|(what is this?)|
Collagenase clostridium histolyticum is an enzyme produced by the bacterium Clostridium histolyticum that dismantles collagen. It is used as a powder-and-solvent injection kit for the treatment for Dupuytren's contracture, a condition where the fingers bend towards the palm and cannot be fully straightened. BioSpecifics Technologies developed the preparation, which is manufactured and marketed by Auxilium Pharmaceuticals and Pfizer as Xiaflex in the US and Xiapex in Europe.
In February 2010, the Food and Drug Administration of the United States approved Xiaflex for the treatment of Dupuytren's contracture. It is the first approved nonsurgical treatment for this condition. In a case of Dupuytren's contracture, collagen accumulates in the palmar fascia of the hands, so that the fingers cannot be straightened. A similar phenomenon occurs in Peyronie's disease, a contracture of the penis.
In February 2011, the European Commission's Committee for Medicinal Products for Human Use approved the product for the treatment of Dupuytren's contracture in adults with a palpable cord by 'properly trained' doctors. Pfizer was reported to be working with Europe's national medicines regulatory bodies to launch the new treatment, hoping doctors could prescribe the treatment by late 2011.
On November 7, 2012, BioSpecifics announced "BioSpecifics Technologies Corp. : Reports Third Quarter 2012 Financial Results". Auxilium's submission of a License Application to the FDA for XIAFLEX for the potential treatment of Peyronie's disease, an excess of inelastic collagen causing penile curvature deformity. If approved by the FDA, which Auxilium anticipates by the end of 2013, XIAFLEX is expected to be the first and only biologic therapy indicated for the treatment of Peyronie's disease. Auxilium also reported additional trials for potential use of Xiaflex are underway for the treatment of Frozen Shoulder, Cellulite reductions and both Human and Canine Lipoma's.
The most common side effects include lymphadenopathy (swollen lymph nodes), itching, pain, oedema, and bleeding (for example in the form of bruises or ecchymoses). Allergic reactions are seen in less than 1% of patients.
The substance is a constant mixture of two collagenases (AUX-I and AUX-II) with known amino acid sequences and a length of about 1000 amino acids each. It is prepared by anaerobic fermentation from a strain of C. histolyticum that has been known since 1950.
The two collagenases act synergistically by cleaving tropocollagen (the 'collagen molecule') at different points. AUX-I attacks the C- and N-termini, AUX-II cleaves amino acid bonds within the molecule. Small collagen fragments are broken down by both enzymes.
No interaction studies have been conducted because the drug does not reach the bloodstream and the liver. It is theorised that drugs interfering with matrix metalloproteinases, such as tetracyclines, anthracyclines, quinolones and anthraquinone derivatives, could reduce the efficacy of the collagenases, but no clinical evidence for such an interaction has been observed.
- "FDA Approves Xiaflex for Debilitating Hand Condition". Food and Drug Administration. February 2, 2010. Retrieved March 16, 2010.
- Pollack, Andrew (March 15, 2010). "Triumph for Drug to Straighten Clenched Fingers". The New York Times. Retrieved March 16, 2010.
- Pollack, Andrew (March 15, 2010). "Bringing Movement Back to Clenched Hands". The New York Times. Retrieved March 16, 2010.
- Xiapex: collagenase clostridium histolyticum, European Medicines Agency, Undated.Accessed: 20 March 2011.
- Xiapex (Collagenase Clostridium Histolyticum) Authorised In The European Union For Dupuytren's Contracture, Medical News Today, Bexhill-on-Sea, East Sussex, 3 March 2011.Accessed: 19 March 2011.
- "Xiaflex for the Treatment of Cellulite".
- Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X.
- A. Klement (9 May 2011). "Dupuytren'sche Kontraktur erstmals medikamentös behandelbar: Xiapex". Österreichische Apothekerzeitung (in German) (10/2011): 8.