Collagenase clostridium histolyticum

Last updated
Collagenase clostridium histolyticum
Clinical data
Trade names Xiaflex, Xiapex, Qwo
Other namesAA-4500, collagenase clostridium histolyticum-aaes
AHFS/Drugs.com Monograph
MedlinePlus a612029
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 InfoCard 100.029.608 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Molar mass 114 kg/mol (AUX-I)
113 kg/mol (AUX-II)
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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.

Contents

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.[ medical citation needed ]

Collagenase clostridium histolyticum injection for Dupuytren's contracture. Before, next day, and two weeks after first treatment Xiaflex (Collagenase) for Dupuytrens.jpg
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[ citation needed ] 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]

Related Research Articles

<span class="mw-page-title-main">Peyronie's disease</span> Medical condition

Peyronie's disease is a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. Specifically, scar tissue forms in the tunica albuginea, the thick sheath of tissue surrounding the corpora cavernosa, causing pain, abnormal curvature, erectile dysfunction, indentation, loss of girth and shortening.

Daclizumab is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells.

<span class="mw-page-title-main">Dupuytren's contracture</span> Disease with gradual bending of the fingers due to scar tissue build-up within the palms

Dupuytren's contracture is a condition in which one or more fingers become permanently bent in a flexed position. It is named after Guillaume Dupuytren, who first described the underlying mechanism of action, followed by the first successful operation in 1831 and publication of the results in The Lancet in 1834. It usually begins as small, hard nodules just under the skin of the palm, then worsens over time until the fingers can no longer be fully straightened. While typically not painful, some aching or itching may be present. The ring finger followed by the little and middle fingers are most commonly affected. It can affect one or both hands. The condition can interfere with activities such as preparing food, writing, putting the hand in a tight pocket, putting on gloves, or shaking hands.

<span class="mw-page-title-main">Hyaluronidase</span> Class of enzymes

Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid (HA). Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluronidases are two classes of eukaryotic endoglycosidase hydrolases and a prokaryotic lyase-type of glycosidase.

<span class="mw-page-title-main">Plantar fibromatosis</span> Medical condition

Plantar fascial fibromatosis, also known as Ledderhose's disease, Morbus Ledderhose, and plantar fibromatosis, is a relatively uncommon non-malignant thickening of the feet's deep connective tissue, or fascia. In the beginning, where nodules start growing in the fascia of the foot the disease is minor. Over time walking becomes painful. The disease is named after Georg Ledderhose, a German surgeon who described the condition for the first time in 1894. A similar disease is Dupuytren's disease, which affects the hand and causes bent hand or fingers.

<span class="mw-page-title-main">Verteporfin</span> Pharmaceutical drug

Verteporfin, a benzoporphyrin derivative, is a medication used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 689 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.

<span class="mw-page-title-main">Rifapentine</span> Chemical compound

Rifapentine, sold under the brand name Priftin, is an antibiotic used in the treatment of tuberculosis. In active tuberculosis it is used together with other antituberculosis medications. In latent tuberculosis it is typically used with isoniazid. It is taken by mouth.

Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as Clostridium. They are considered a virulence factor, facilitating the spread of gas gangrene. They normally target the connective tissue in muscle cells and other body organs.

Microbial collagenase is an enzyme. This enzyme catalyses the following chemical reaction

Mepolizumab, sold under the brand name Nucala, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis, and hypereosinophilic syndrome (HES). It recognizes and blocks interleukin-5 (IL-5), a signalling protein of the immune system.

A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate, or PO4, group) to a protein and can modulate its function.

<span class="mw-page-title-main">Oritavancin</span> Pharmaceutical drug

Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.

<span class="mw-page-title-main">Miglustat</span> Medication used to treat Gaucher disease

Miglustat, sold under the brand name Zavesca, is a medication used to treat type I Gaucher disease (GD1). It is also known as N-butyldeoxynojirimycin, and is a derivative of the anti-diabetic 1-deoxynojirimycin. It was developed by Oxford GlycoSciences and is marketed by Actelion.

Velaglucerase alfa, sold under the brand name Vpriv, is a medication used for the treatment of Gaucher disease Type 1. It is a hydrolytic lysosomal glucocerebroside-specific enzyme, which is a recombinant form of glucocerebrosidase. It has an identical amino acid sequence to the naturally occurring enzyme. It is manufactured by Shire plc.

<span class="mw-page-title-main">Pirfenidone</span> Chemical compound

Pirfenidone, sold under the brand name Pirespa among others, is a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.

Hathewaya histolytica is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. H. histolytica is pathogenic in many species, including guinea pigs, mice, and rabbits, and humans. H. histolytica has been shown to cause gas gangrene, often in association with other bacteria species.

Clostridial aminopeptidase is an enzyme. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Ines Mandl</span> Austrian-born American biochemist

Ines Mandl was an Austrian-born American biochemist who was awarded the Garvan-Olin Medal in 1983 for her work on the enzyme collagenase. She was a professor at Columbia University.

Emapalumab, sold under the brand name Gamifant, is an anti-interferon-gamma (IFNγ) antibody medication used for the treatment of hemophagocytic lymphohistiocytosis (HLH), which has no cure.

Cerliponase alfa, marketed as Brineura, is an enzyme replacement treatment for Batten disease, a neurodegenerative lysosomal storage disease. Specifically, Cerliponase alfa is meant to slow loss of motor function in symptomatic children over three years old with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). The disease is also known as tripeptidyl peptidase-1 (TPP1) deficiency, a soluble lysosomal enzyme deficiency. Approved by the United States Food and Drug Administration (FDA) on 27 April 2017, this is the first treatment for a neuronal ceroid lipofuscinosis of its kind, acting to slow disease progression rather than palliatively treat symptoms by giving patients the TPP1 enzyme they are lacking.

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. "Xiapex". 17 September 2018.
  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. 1 2 3 Haberfeld H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN   978-3-85200-196-8.
  12. 1 2 Klement A (9 May 2011). "Dupuytren'sche Kontraktur erstmals medikamentös behandelbar: Xiapex". Österreichische Apothekerzeitung (in German) (10/2011): 8.