Systemic lupus erythematosus - abetimus sodium
Systemic lupus erythematosus is a chronic inflammatory disease of the connective tissue. It affects the skin and various internal organs, usually leading to a red, scaly rash on the face, particularly the nose and cheeks, plus arthritis and progressive kidney damage. It can also affect the brain, heart and lungs, with progressive attacks of inflammation, followed by the formation of scar tissue.
It is an autoimmune disease, usually treated by corticosteroids or immunosuppressant drugs. A new agent to treat lupus, and particularly lupus renal disease, is being developed by La Jolla Pharmaceuticals. Abetimus sodium, formerly referred to as LJP 394, is a tetrakis-oligonucleotide conjugate that acts as an immunomodulating agent by inducing tolerance in B cells, directed against double-stranded DNA, which it does by crosslinking surface antibodies.
To evaluate its safety and tolerability, a multicentre, partially randomised, placebo controlled, double blind, dose ranging trial was carried out.1 A total of 58 patients were given 1, 10 or 50mg of the drug or placebo at weekly, biweekly or monthly intervals for a total of 17 weeks. Those given the highest dose had the greatest reduction in mean dsDNA antibody titres.
In a randomised double blind placebo controlled trial, 230 patients lupus patients with a history of renal disease were randomised to 16 weekly doses of 100mg abetimus or placebo, followed by alternating eight week drug holidays and 12 weekly doses of 50mg abetimus or placebo, for a total of 76 weeks.2 The delay before treatment with high-dose corticosteroids and/or cyclophosphamide (HDCC) was longer in those given the active, and they required 41% fewer treatment with this HDCC. In those patients with high affinity antibodies, this time was longer, and 62% fewer treatments were needed. The drug was also well tolerated. Abetimus has been granted orphan drug status by both the EU and the US FDA, and trials testing its therapeutic usefulness continue.