Clinical and pharmacological experience with LJP-394.

LJP-394 is a synthetic biological with immunomodulatory functions. Composed of four double-stranded oligodeoxynucleotides attached to a central branched platform, the drug acts as an anti-"anti-ds-DNA" B-cell toleragen by rendering specific B-lymphocytes unresponsive to immunogen so they do not produce autoantibodies. Extensive animal studies and Phase II clinical trials suggested that the effects of LJP-394 are effective and safe when used as a weekly dose of 100 mg intravenously. Analysis of a multicentre, international Phase II/III clinical trial showed that patients with lupus nephritis and high affinity IgG antibodies to LJP-394 have clinical benefits. This includes increased time to renal flares, reduced number of renal flares, time to institution of high-dose corticosteroids and/or cyclophosphamide and lower anti-ds-DNA levels. A definitive trial is in progress. LJP-394 appears to be free of serious adverse reactions. Though promising, the role of LJP-394 in patients with active, organ-threatening lupus is still not known.