Product case study Kepivance

Kepivance (tradename, also known as palifermin) is a keratinocyte growth factor produced by recombinant means in E. coli. It was first approved in the USA in 2004 and is indicated to decrease the incidence and duration of severe oral mucositis in patients with haematologic malignancies receiving myelotoxic therapy requiring haematopoietic stem cell support. Oral mucositis, characterized by ulcerative lesions of the mouth, is a common and debilitating side effect of high-dose chemotherapy or radiotherapy. It is particularly common (incidence of 70-80 per cent) and severe in the indication patient grouping.

Keratinocyte growth factor is a 140 amino acid, 16.3 kDa member of the FGF family. It differs from native keratinocyte growth factor in that the first 23 N-terminal amino acids have been deleted, which improves its stability. After cell growth the product is recovered and purified by a multistep chromatographic protocol. It is presented in lyophilized format in single-use vials and containing mannitol, sucrose, polysorbate 20 and histidine as excipients. It is administered by daily i.v. injection, usually for several days.

The cell surface keratinocyte growth factor receptor is present in a wide variety of tissues, including the tongue, buccal mucosa and oesophagus, but also additional tissues including the liver, kidneys and bladder. Keratinocyte growth factor receptor binding triggers proliferation, differentiation and migration of epithelial cells.

After single-dose i.v. administration, total body clearance appears two- to four-fold higher in cancer patients than in healthy subjects, although elimination half-life (3.3-5.7 h) was similar in both groups.

The initial trial establishing safety and efficacy was a randomized, placebo-controlled study involving 212 patients. The treated group received 60 ^g kg-1 day-1 of the product for 6 days. The primary end-point measured was the number of days during which the patients experienced severe oral mucositis, which treatment reduced from 9 to 3 days. The incidence of mucositis was also reduced from 98 per cent to 63 per cent.

Side effects noted included rash, erythema, tongue thickening and discoloration, as well as alteration of taste. Kepivance is manufactured and marketed by Amgen Inc.

consists of three separate growth factors: TGF-P1, -P2 and -P3. Although the product of distinct genes, all exhibit close homology. In the mature form, they exist as homodimers, with each subunit containing 112 amino acid residues. Most body cells synthesize TGF-P, singly or in combination.

TGF-Ps are pleiotrophic cytokines. They are capable of inhibiting the cell cycle and, hence, cell growth of several cell types, most notably epithelial and haematopoietic cells. These factors, however, stimulate the growth of other cell types, most notably cells that give rise to connective tissue, cartilage and bone. They induce the synthesis of extracellular matrix proteins and modulate the expression of matrix proteases. They also serve as a powerful chemoattractant for monocytes and fibroblasts. Given such activities, it is not surprising that the major physiological impact of TGF-Ps appears to relate to:

• tissue remodelling;

• haemopoiesis.

Such activities render them potentially useful therapeutic agents, and several are being assessed medically.

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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