Antiamyloidogenic agent - eprodisate sodium
Amyloid A amyloidosis is a rare complication that can occur in patients with chronic inflammatory disorders.
Amyloid A amyloidosis is a rare complication that can occur in patients with chronic inflammatory disorders.
Insoluble misfolded serum amyloid A protein is deposited as extracellular plaques in various organs, notably the spleen and kidneys, but also others such as the skin, intestines, heart and blood vessel walls. It is a progressive condition and, left untreated, is generally fatal.
Serum amyloid A is produced by the liver in response to inflammatory cytokines, and levels would normally return to normal after injury or infection within a week. But in some chronic inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis, and also in chronic infections like tuberculosis, the levels remain high. About 10% of these patients will develop amyloid A amyloidosis, when the amyloid A is partially denatured by heparin sulfate and refolds in a more stable form that cross-polymerises and is deposited as insoluble fibrils.
The first drug to be developed that treats the condition is Neurochem's eprodisate sodium, which has been licensed to Centocor for distribution;1 current treatment focuses on addressing the underlying inflammation, and organ transplantation when it becomes necessary. The drug prevents the misfolding in vitro, and was shown to reduce amyloid A plaque formation in mouse models.
A two year Phase II/III clinical trial was carried out in 183 patients with amyloid A amyloidosis, who were randomised to receive eprodisate or placebo.2 Those given the drug had a 42% reduction in the risk of death or worsening of kidney function than the group given placebo, and 13.4% fewer of those given the drug had disease worsening. The drug was well tolerated, with the incidence and severity of adverse events being similar between the two groups.
After two years, 80% of the patients continued in an open label extension of the study. One year on, those who had received the drug for three years were 41% less likely to have died or have impaired renal function compared to those who switched to the active for the third year.