SLE TRIAL SHOWS FEWER RENAL FLARES IN LJP 394-TREATED PATIENTS WITH HIGH-AFFINITY ANTIBODIES TO LJP 394: 90-05 TRIAL RESULTS

D Alarcon-Segovia, J Tumlin, R Furie, J McKay, M Cardiel, M Linnik, B Hepburn.
La Jolla Pharmaceutical Co., San Diego, CA, USA.

Introduction: LJP 394 contains four 20 mer dsDNA epitopes attached to an inert platform. It binds dsDNA antibodies and is designed to induce B cell tolerance.

Objective: This trial was designed to compare the ability of LJP 394 and placebo (PBO) to prevent renal flares (delay time to renal flare), reduce aDNA, and decrease high-dose corticosteroid and cyclophosphamide (HDCC) treatment.

Methods: Patients with aDNA and a history of SLE renal flare received weekly infusions of PBO or 100mg of LJP 394 for 16 wks, followed by intermittent dosing with PBO or 50mg of LJP 394 for 60 wks. A renal flare was recorded if there was a significant and reproducible increase in serum creatinine, proteinuria or hematuria that was attributed to SLE by the physician.

Results: The trial enrolled 230 patients and was stopped after an interim analysis showed 19 renal flares in the drug group and 23 in the PBO group. Patients' pretreatment antibodies were analyzed for affinity to the drug. In the 89% of patients with high-affinity for drug, there were 7 flares in the drug group and 21 in the PBO group (p<0.01). Time to renal flare was longer in drug-treated patients with high-affinity antibodies (p<0.01). The drug group was exposed to less HDCC in the intent-to-treat population (p<0.05) and high-affinity subpopulation (p<0.01).

Conclusion: LJP 394 appeared to provide clinical benefit to the 89% of patients with high-affinity antibodies to its dsDNA epitope. The drug was well tolerated.

Presented at
The 6th International Lupus Conference
Barcelona, Spain
March 24-28, 2001