INTEGRATED SAFETY RESULTS FROM STUDIES OF LJP394 IN SLE PATIENTS

Claudia Hura, MD1, JA Tumlin, MD2, and K R Heilbrunn, MD3

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

Integrated analyses were performed on safety data from SLE pts who received 100mg LJP394 once a week in randomized, placebo controlled trials (RCT) of LJP394 in SLE patients (pts).
The majority of safety data comes from a Phase 2/3 RCT (pts treated for up to 18 months; 16 weeks 100mg LJP394 or placebo [pbo] weekly followed by 3 cycles of 8 weeks drug holiday and 12 weeks 50mg LJP394 or pbo) and a Phase 3 RCT (pts treated for up to 22 months; 100mg LJP394 or pbo weekly), which enrolled 230 and 317 pts, respectively. Pts had SLE, a history of renal disease, and anti-dsDNA antibody levels > 15 IU/mL at screening (Farr). Additional safety information provided from an ECG effect study where healthy volunteers received a single dose of LJP394 up to 300mg.

419 SLE pts were exposed to 100mg LJP394. 81 pts have been exposed to 100mg LJP394 for at least a 1 year treatment period. There were no significant differences in baseline demographics between LJP394 or pbo treated pts. 88% (369/419) of pts who received 100mg weekly LJP394 and 89% (263/296) in the pbo group experienced at least 1 adverse event (AE). The most frequently reported AE in both treatment groups were in the system "body as a whole". 17% (70/419) of pts who received 100mg weekly LJP394 experienced serious adverse events (SAE). 16% (46/296) of pbo treated pts experienced SAEs. 3% of pts (14/419) in the LJP394 100mg group had a SAE that led to withdrawal from study drug compared to 3% (9/296) of pts in the pbo group. No clinically relevant effect on QT prolongation in healthy volunteers who received a single dose of LJP394 up to 300mg in the ECG study was seen.

The safety of LJP394 has been evaluated in 13 clinical studies conducted in 614 SLE pts and healthy volunteers exposed to LJP394. Weekly administration of 100mg LJP394 for periods of up to 22 months appeared to be well tolerated. There were no apparent differences in the overall incidence of AE or SAE between LJP394 and pbo treated pts. The demonstrated safety profile may derive from the high degree of specificity inherent in the structure of LJP394, which consists of 97% native phosphodiester dsDNA.

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