Collagenase clostridium histolyticum

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 of Dupuytren's contracture, a condition where the fingers bend towards the palm and cannot be fully straightened, and Peyronie's disease, a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. BioSpecifics Technologies developed the preparation, which is manufactured and marketed by Endo Pharmaceuticals as Xiaflex in the US and by Sobi as Xiapex in Europe.

Collagenase clostridium histolyticum
Clinical data
Trade namesXiaflex, Xiapex, Qwo
Other namesAA-4500, collagenase clostridium histolyticum-aaes
AHFS/Drugs.comMonograph
MedlinePlusa612029
License data
Routes of
administration		Intralesional injection
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem SID
DrugBank
ChemSpider
  • none
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.029.608
Chemical and physical data
Molar mass114 kg/mol (AUX-I)
113 kg/mol (AUX-II)
 NY (what is this?)  (verify)

Biochemically, it is a mixture of two C. histolyticum collagenases, ColH and ColG. A similar ointment preparation called Santyl contains one or many collagenases from the same bacterium, but it is unclear which.[1]

Uses

In February 2010, the Food and Drug Administration of the United States approved Xiaflex for the treatment of Dupuytren's contracture.[2][3] It is the first approved nonsurgical treatment for this condition.[4] 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.

Collagenase clostridium histolyticum injection for Dupuytren's contracture. Before, next day, and two weeks after first treatment

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.[5] 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.[6] However, the Swedish manufacturer abruptly withdrew distribution of this drug in Europe in March 2020 for commercial reasons.[7] Collagenase is no longer available on the National Health System except as part of a small clinical trial.[8]

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. The FDA approved Xiaflex for the treatment of Peyronie’s disease in December 2013. Following this, Xiapex gained EU approval for the treatment of Peyronie’s disease in February 2015, making it the first and only biologic therapy indicated for the treatment of Peyronie's disease.[9] Auxilium has also reported additional trials for potential use of Xiaflex are underway for the treatment of frozen shoulder, cellulite reductions and both human and canine lipomas.[10]

Side effects

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.[11]

Chemical properties

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.[12]

Pharmacology

The enzymes do not reach the bloodstream in significant amounts and are presumed to largely stay at the point of injection[11] until they are broken down by proteases.

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.[12]

Interactions

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.[11]

References
  1. "Collagenase ColH of Hathewaya histolytica (Clostridium histolyticum) [Q46085]". UniProt. Retrieved 26 December 2020.
  2. "FDA Approves Xiaflex for Debilitating Hand Condition". Food and Drug Administration. February 2, 2010. Archived from the original on November 26, 2012. Retrieved March 16, 2010.
  3. Pollack A (March 15, 2010). "Triumph for Drug to Straighten Clenched Fingers". The New York Times. Retrieved March 16, 2010.
  4. Pollack A (March 15, 2010). "Bringing Movement Back to Clenched Hands". The New York Times. Retrieved March 16, 2010.
  5. Xiapex: collagenase clostridium histolyticum, European Medicines Agency, Undated.Accessed: 20 March 2011.
  6. 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.
  7. https://www.ema.europa.eu/en/medicines/human/EPAR/xiapex
  8. "Dupuytren's Interventions: Surgery vs Collagenase - Trials and Statistics, University of York".
  9. Xiapex summary of product characteristics
  10. "Xiaflex for the Treatment of Cellulite".
  11. Haberfeld H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 978-3-85200-196-8.
  12. Klement A (9 May 2011). "Dupuytren'sche Kontraktur erstmals medikamentös behandelbar: Xiapex". Österreichische Apothekerzeitung (in German) (10/2011): 8.
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