UCB and Biogen Present New Phase 3 Dapirolizumab Pegol Results in SLE

UCB and Biogen presented new analyses from the Phase 3 PHOENYCS GO (NCT04294667) program at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress, providing further evidence that dapirolizumab pegol (DZP) may help patients with systemic lupus erythematosus (SLE) maintain disease control while reducing long-term glucocorticoid use.

The findings expand on previously reported Phase 3 results and address a key treatment goal in SLE, where prolonged steroid exposure contributes to cumulative toxicity, organ damage, and increased morbidity.

Mechanism and Disease Context

Dapirolizumab pegol is an investigational PEG-conjugated, Fc-free anti-CD40 ligand (CD40L) antibody fragment. By inhibiting CD40L signaling, DZP reduces B-cell activation, autoantibody production, type I interferon activity, and broader immune-cell activation involved in SLE pathogenesis.

SLE is a chronic autoimmune disease that can affect multiple organs and is characterized by periods of increased disease activity, or flares, which may lead to irreversible organ damage over time.

Steroid Reduction and Clinical Outcomes

A post hoc analysis evaluated patients receiving more than 7.5 mg/day prednisone-equivalent glucocorticoids at baseline. Patients treated with DZP plus standard of care were more likely than those receiving placebo plus standard of care to taper glucocorticoids to 7.5 mg/day or less while maintaining disease control through Week 48.

Investigators also reported higher rates of sustained steroid reduction among patients who achieved key clinical outcomes, including British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response, Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response, and freedom from moderate or severe BILAG-2004 flares.

Immunological and Flare Outcomes

Additional analyses presented at EULAR showed reductions in anti-double-stranded DNA (anti-dsDNA) antibodies and increases in complement proteins C3 and C4 among patients with abnormal baseline levels. Researchers also observed lower rates of moderate and moderate-to-severe BILAG-2004 flares through Week 48 compared with placebo, supporting DZP’s activity across multiple measures of disease control.

The program further explored patient-reported outcomes, highlighting fatigue as a major burden for patients and emphasizing the need for assessment tools that capture disease impact beyond traditional clinical measures.

Safety Findings

Safety findings were consistent with previous studies. Treatment-emergent adverse events occurred more frequently with DZP than placebo, while serious adverse events were less common and discontinuations remained low in both groups.

Clinical Implications

Megan E.B. Clowse, MD, MPH, of Duke University noted that cumulative steroid exposure and uncontrolled disease activity remain major drivers of organ damage and poor outcomes in SLE.

Donatello Crocetta, Chief Medical Officer at UCB, said the findings support the potential of DZP to reduce long-term glucocorticoid use while maintaining disease control.

Biogen’s Diana Gallagher, MD, highlighted the therapy’s effects across clinical, biological, and patient-reported outcomes.

The EULAR presentations follow the recent publication of PHOENYCS GO results in The Lancet, which reported clinically meaningful improvements in disease activity at Week 48.

Ongoing Development

DZP remains investigational and has not been approved by any regulatory authority. UCB and Biogen are continuing development through the Phase 3 PHOENYCS FLY study (NCT06617325), which could support future regulatory submissions and further define the therapy’s role in SLE treatment.

Reference

EULAR 2026: Dapirolizumab Pegol Shows Potential to Reduce Flare Rates and Maintain Disease Control in Systemic Lupus Erythematosus | Biogen