SUMMARY OF SAFETY RESULTS FROM STUDIES OF LJP 394 IN SLE PATIENTS

S. Bombardieri, M. A. Cardiel, J. A. Tumlin, R. A. Furie, D. J. Wallace, C. Hura, M. Schneider, F. Hiepe, V. Strand, T. Joh, T. Foster, I. Yushmanova, K. R. Heilbrunn

Background: To summarize safety data generated from randomized, placebo controlled trials (RCTs) of LJP 394 in SLE patients (pts). LJP 394 is a novel, immunomodulatory agent designed to specifically reduce anti-dsDNA antibody levels and thereby delay the time to, and reduce the incidence of, renal flares and Major SLE flares. This assessment includes data from pts who were in RCTs who received weekly dosing with 100mg LJP 394.

Methods: The majority of the safety data generated on LJP 394 comes from the Phase 2/3 RCT (pts treated for up to 18 months; 16 wks 100mg LJP 394 or placebo [pbo] wkly followed by 3 cycles of 8 wks drug holiday and 12 wks 50mg LJP 394 or pbo) and the Phase 3 RCT (pts treated for up to 22 months; 100mg LJP 394 or pbo wkly), which enrolled 230 and 317 pts respectively. Study pts had SLE, a history of renal disease, and had anti-dsDNA antibody levels ≥15 IU/mL at screening (Farr). Because of the morbidity and mortality associated with SLE, pts were permitted to receive concomitant immunosuppressive agents (IAs) during the trial. Pts on cyclophosphamide were excluded. The safety population includes all randomized pts. Safety data were also generated on pts who had high-affinty antibodies (HA abs) to LJP 394 at baseline, the targeted treatment population, retrospectively identified in the Phase 2/3 RCT and prospectively in the Phase 3 RCT.

Results: Baseline characteristics were similar for the 2 treatment arms in both RCTs. In the Phase 2/3 and Phase 3 RCTs > 75% of pts were on prednisone and > 34% were on IAs other than prednisone at baseline. Of pts who received 100 mg wkly in RCTs, 88% pts in the LJP 394 group and 89% pts in the pbo group experienced at least 1 adverse event. Forty-three pts (15%) experienced serious adverse events while receiving LJP 394 100 mg in the placebo-controlled studies compared with 46 pts (16%) in the pbo group. Three pts in the LJP 394 100 mg group and 3 pts in the pbo group experienced serious AE’s considered by the Investigator to be possibly related to study drug. There were 3 deaths in the LJP 394 group and 2 in the pbo group that occurred during the study or within 30 days of final dose. None of the deaths were considered to be related to treatment with study drug. Withdrawals from the studies due to an adverse event occurred in 13 patients (4.8%) treated with LJP 394 and 13 patients (4.7%) in the pbo group. The incidence of AEs and SAEs was similar between the group of pts with HA abs and all pts in pbo-controlled studies.

Conclusion: Administration of LJP 394 for periods of up to 22 months appeared to be well tolerated. The demonstrated safety profile is believed to be related to the high degree of specificity inherent in the structure of LJP 394, which consists of 97% native phosphodiester dsDNA.

Presented at the
Annual European Congress of Rheumatology "EULAR 2004"
Berlin, Germany
June 9 –12, 2004