Dapirolizumab pegol for systemic lupus shows efficacy signal

Patients with systemic lupus erythematosus (SLE) appear to exhibit improvements with dapirolizumab pegol (DZP) in a phase IIb trial, which, however, did not meet its primary endpoint.

A total of 182 adult patients were randomized to receive treatment with placebo or intravenous DZP (6/24/45 mg/kg) in addition to standard of care (SOC) every 4 weeks up to week 24. After this, they were given SOC through week 48.

All patients had moderately to severely active SLE (SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6 and ≥1 British Isles Lupus Assessment Group [BILAG] A or ≥2 BILAG B domain scores), receiving stable corticosteroid (≤40 mg/day prednisone-equivalent), antimalarial, or immunosuppressant drugs. Some had stable lupus nephritis (proteinuria ≤2 g/day) and not on high-dose corticosteroids or cyclophosphamide.

A total of 178 (97.8 percent) patients completed the double-blind treatment, while 164 (90.1 percent) completed the observational period. The primary outcome of a dose-response relationship based on week 24 BILAG-Based Composite Lupus Assessment (BICLA) responder rates was not achieved.

Nevertheless, DZP-treated patients showed improvements in clinical and immunological outcomes compared with those on placebo at week 24.

DZP seemed well tolerated. Serious treatment-emergent adverse events occurred with similar frequency across all treatment groups.

During the observation period, scores for SLEDAI-2K, physician’s global assessment (PGA), BILAG, and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) stabilized. On the other hand, BICLA and SLE Responder Index (SRI-4) responder rates dropped, possibly because of prohibition of escape medications. BILAG flares also increased, while immunologic parameters returned to baseline levels.

The potential clinical benefit of DZP warrants further evaluation.