REDUCTIONS IN 24-HOUR URINE PROTEIN LEVELS ASSOCIATED WITH TREATMENT OF SLE PATIENTS WITH LJP394 IN TWO RANDOMIZED, PLACEBO-CONTROLLED CLINICAL TRIALS

James A Tumlin, MD1, Claudia Hura, MD2, Tenshang Joh3 and Kenneth R Heilbrunn, MD3

1 Emory Univ, Atlanta, GA; 2 San Antonio Kidney Disease Ctr, San Antonio, TX; 3 La Jolla Pharmaceutical, San Diego, CA

The treatment effect of LJP394 on 24-hour urine protein levels was evaluated in two randomized, placebo-controlled trials (RCT) in SLE patients (pts) with a history of renal disease.

The pts had a diagnosis of SLE, a history of renal flare within the past 4 years, and elevated dsDNA antibody levels (Farr ≥15 IU/mL) during screening. The analysis population consisted of SLE patients with high-affinity antibodies to the oligonucleotide epitope of LJP 394 at baseline, defined retrospectively in the Phase 2/3 RCT and prospectively in the Phase 3 RCT. The Phase 2/3 RCT enrolled 189 HA pts (92 LJP394; 97 placebo [pbo]) who were treated for up to 18 months (16 doses of 100 mg LJP394 or pbo weekly followed by 3 cycles of an 8 week drug holiday and 12 doses of 50 mg LJP394 or pbo weekly). The Phase 3 RCT enrolled 298 HA pts (145 LJP394; 153 pbo) who were treated weekly for up to 22 months (100 mg LJP394 or pbo). Changes in proteinuria were analyzed for pts who had 24-hour urine collections both at baseline and at approximately 1 year using logistic regression. 42% (79/189) and 45% (135/298) of pts had urine collections at both these time points in the Phase 2/3 and Phase 3 RCTs, respectively.
In the Phase 2/3 RCT, 44.2% (23/52) of pts in the LJP394 group demonstrated a 50% reduction in 24-hour urine protein from baseline at week 52 compared to 18.0% (11/61) in the pbo group (nominal p = 0.002). In the Phase 3 RCT, 41.3% (26/63) of pts in the LJP394 group demonstrated a 50% reduction in 24-hour urine protein from baseline at week 52 compared to 28.4% (23/81) in the pbo group (nominal p = 0.047).

Progression of SLE-related renal disease is often associated with increasing proteinuria. Reducing proteinuria is an important goal in both the preservation of renal function and in the overall management of these pts. Treatment with LJP394 may reduce proteinuria in SLE pts with a history of renal disease.

Presented at the
American Society of Nephrology Annual Scientific Meeting
St. Louis, MO
Oct. 27-Nov. 1, 2004