Mucositis iseganan
Around three quarters of all patients undergoing high dose chemotherapy and radiotherapy treatment for cancer will develop the side-effect mucositis. In patients with this condition, the rate of cell renewal of the basal epithelial cells in the oral mucosa is reduced, leaving the mucosa thinned and much more susceptible to ulceration. Any resulting systemic infections can be life threatening in already ill patients.
Antibiotics are an option for oral mucositis, and protegrins are being investigated for this indication. Five naturally occurring protegrins have been identified, with between 16 and 18 amino acids. All have a cysteine residue at each of positions 6, 8, 13 and 15 on the chain, which form disulphide bonds that maintain the molecule's secondary structure. Protegrins are active against a variety of different bacteria, both Gram positive and Gram negative. They have a rapid onset of action, and minimal resistance to protegrins has thus far been observed in bacteria.
US company IntraBiotics Pharmaceuticals has developed a protegrin analogue that has promise as a medicine. Iseganan hydrochloride, formerly referred to as IB 367, is a 17 amino acid peptide that is active against oral microflora.1 In a Phase II randomised, double blind, placebo-controlled study, patients undergoing myeloablative chemotherapy and bone marrow transplantation were treated with a 9mg oral rinse every four hours. It reduced the severity of oral mucositis by an average of 22% in total, and by 40% in the 76 patients who used the rinse at least three days before the transplant took place.2
A randomised double blind, placebo-controlled Phase III study was carried out in patients undergoing high dose myeloablative chemotherapy. They were given an oral solution of the drug, and the pain they were experiencing evaluated on a scale of 1 to 10, three times a week for three weeks.3 323 patients were evaluated; 15% on placebo and 5% receiving iseganan reported pain scores of 9 or 10
A further Phase III randomised double blind, placebo controlled, multinational trial is under way, with patients either receiving iseganan as an oral rinse, or placebo.
The molecule is also being investigated in a Phase IIa study as a treatment for hospital-acquired bacterial pneumonia in patients who are on ventilators, and also in a Phase I trial for respiratory infections that develop in cystic fibrosis sufferers.