Abetimus

General information

Abetimus is a selective immunomodulator for the treatment of systemic lupus erythematosus. It induces tolerance in B lymphocytes directed against double-stranded DNA by cross-linking surface antibodies. It also reduces serum double-stranded DNA antibodies and splenic double-stranded DNA antibody-producing cells in BXSB mice, giving improved renal function and histopathology, as well as prolonged survival [ ].

In a phase-2, partly randomized, double-blind, placebo-controlled study of three different doses of abetimus in 58 patients, seven did not receive all doses because of adverse events [ ]. Five withdrew because of adverse events related to their lupus erythematosus: non-renal exacerbations (n = 2), hematuria and hypertension (n = 1), worsening rash (n = 1), and nephritis (n = 1). One patient withdrew because of cellulitis and another because of a localized Herpes zoster infection. None of the reported adverse events was considered to be definitely related to the drug.

Subsequently, La Jolla Pharmaceuticals terminated two previously established licensing agreements for abetimus [ ]. One of the agreements was with Leo Pharmaceutical Products of Denmark, which was licensed to market abetimus in Europe and the Middle East, and the other was with Abbott Laboratories. Abbott returned all rights to abetimus to La Jolla Pharmaceuticals in September 1999, based on the results of an analysis of a phase-2/phase-3 trial of abetimus in patients with systemic lupus erythematosus and a history of renal disease, which had been stopped in May 1999 because the primary end-point (the time to worsening of renal function) was much shorter than expected. A further analysis then showed that the number of exacerbations in responders treated with abetimus was less than half the number in the patients treated with placebo. Responders also had a significant reduction in the use of high-dose glucocorticoids and cyclophosphamide.

Another phase-3 placebo-controlled trial called PEARL (Program Enabling Antibody Reduction in Lupus) was conducted in the USA in 317 patients with lupus nephritis, who were treated with abetimus 100 mg/week. The trial was completed in December 2002 and preliminary results were reported in February 2003. However, in April 2003, La Jolla Pharmaceuticals ended the trial, in order to conserve resources for the continued development of the drug.

In September 2000, the US FDA granted orphan drug status to abetimus for the treatment of lupus nephritis; the EU did likewise in November 2001.