Palifermin (trade name Kepivance, marketed by Biovitrum) is a truncated human recombinant keratinocyte growth factor (KGF) produced in Escherichia coli. KGF stimulates the growth of cells that line the surface of the mouth and intestinal tract.

Therapeutic use(s)

When patients with blood cancers (leukemia and lymphoma) receive high dose chemotherapy and radiation therapy to undergo bone marrow transplantation, they usually get severe oral mucositis. Palifermin reduces the incidence and duration of severe oral mucositis by protecting those cells and stimulating the growth of new epithelial cells to build up the mucosal barrier. Palifermin is also being studied in the prevention and treatment of oral mucositis and dysphagia (difficulty swallowing) in other types of cancer.

Drug target and mechanism of action

Keratinocyte growth factor (KGF) resides in the family of fibroblast growth factor (FGF). The drug's target is the KGF receptor. Through the binding of this drug to the aforementioned receptor, Palifermin stimulates epithelial cell proliferation, differentiation, and upregulation of cytoprotective mechanisms to reduce the symptoms of oral mucositis.

Side effects

Common side effects often seen in conjunction with the use of Palifermin include, but are not limited to: • Swelling • Pain (including joint pain) • Increase in blood pancreas enzymes • Increased blood pressure • Proteinuria Some of the more serious side effects can be seen below: • Difficulty breathing • Changes in cutaneous or mucous membrane appearance/feel (redness/rash, swelling, itching, change in color or thickness of tongue, changes in taste) • Fever

Administration

Palifermin is administered via intravenous bolus injection. The drug comes as a lyophilized powder that must be reconstituted with sterile water for injection before it may be administered. It is given for three days before, and three days after chemotherapy is undergone. However, it is important that the drug is not administered within 24 hours of the actual chemotherapy process. This drug is most commonly dosed in a hospital setting, but can be taken at home as per specific instructions regarding preparation and storage from a doctor. The recommended dosage consists of 60 μg/kg/day.

Drug interactions

Co-administration of Palifermin with Heparin should be avoided. Drug interactions with Heparin include a significantly increased systemic exposure to Palifermin. Avoid administration of Palifermin within 24 hours of myelotoxic chemotherapy, as this could result in increased oral mucositis.

Pre-clinical trials

Toxicology studies

Toxicology studies were conducted by use of animal models, utilizing a variety of species, including mice, rats, and monkeys. Singles doses in rats and monkeys were given up to 30,000 and 50,000 micrograms/kg, respectively. Daily doses of 1,000 and 300 micrograms/kg, respectively, were given to rats and monkeys for 28 consecutive days. Toxic effects noted included exaggerated pharmacological effects of the drug, such as hyperkeratosis of skin and tongue and goblet cell hyperplasia in the GI tract. It was noted that the rats were more sensitive to these effects than the monkeys. Induced genetic abnormality assays including microchromosome reverse mutation and E. coli mutagenicity assays were completed using mice. There were no genotoxic effects noted from this study.

Clinical trials

Phase I

Phase II

Phase III

Costs

Palifermin costs approximately 5,000 euros per treatment for a 70 kg patient.

Annual sales

The worldwide profits for years the 2008–2011 are provided below.