Dapirolizumab Pegol Shows Disease Activity Reduction and Fatigue Improvement in SLE at EULAR 2025
UCB and Biogen today presented additional and detailed results from the Phase 3 PHOENYCS GO study evaluating dapirolizumab pegol (DZP), a novel, Fc-free, anti-CD40 Ligand (anti-CD40L) biologic candidate for the treatment of Systemic Lupus Erythematosus (SLE). The data, presented at the annual European Alliance of Associations for Rheumatology (EULAR 2025) congress in Barcelona, Spain, show that dapirolizumab pegol resulted in significant and clinically meaningful improvements in disease activity while addressing a major symptom that profoundly impacts patients’ daily lives — fatigue.
Dapirolizumab pegol is currently an investigational medication and is not yet approved for use by any health authority. The safety and efficacy profile for dapirolizumab pegol in SLE are still under investigation, with a second Phase 3 study underway to confirm these results.
Disease Activity Improvement at Week 48 — Primary Endpoint Met
The Phase 3 PHOENYCS GO study, a multicenter, double-blind, placebo-controlled trial, investigated dapirolizumab pegol’s ability to reduce disease activity in people living with SLE, a complex, chronic autoimmune disease predominantly affecting women. Disease activity in SLE can manifest in many forms — rash, arthritis, kidney abnormalities, hematologic disorders — making its control a major treatment challenge.
At 48 weeks, dapirolizumab pegol demonstrated a significant improvement in disease activity, as measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) — the study’s primary endpoint — when added to standard of care (SOC) treatment. This improvement signals a powerful and consistent therapeutic activity for dapirolizumab pegol in reducing disease severity alongside standard treatments.
Additional secondary endpoints related to disease activity were also improved, alongside measures related to both fatigue and disease remission — two outcomes that remain elusive in the current standard of care.
Improvement in Fatigue — An Unmet Need in SLE
While much progress has been made in developing treatments for SLE, addressing its symptoms’ daily impact — especially fatigue — remained a significant challenge for both patients and clinicians. Fatigue in SLE is frequently persistent, severe, and a major contributor to reduced quality of life. Importantly, this symptom cannot be adequately captured by disease activity scores and often goes underrecognized and undertreated.
“Fatigue is a difficult symptom to treat and a significant contributor to poor quality of life for people living with SLE, even when disease activity is well-controlled,” said Ioannis Parodis, MD, PhD, Associate Professor of Rheumatology at Karolinska University Hospital in Sweden. “The data we’re seeing in this Phase 3 study suggest dapirolizumab pegol may enable a significant improvement in both disease activity and this difficult symptom — offering new hope for patients whose daily routines and well-being are disrupted by persistent fatigue.”
An extensive analysis of patient-reported outcomes related to fatigue further underscores dapirolizumab pegol’s potential in improving this symptom. Among people receiving dapirolizumab pegol alongside standard of care:
- Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores improved by an average of 8.9 points from baseline, significantly greater than the 5.2 point improvement for standard of care alone (nominal p = 0.0024) at Week 48.
- The FATIGUE-PRO scale — a patient-centric tool designed to comprehensively gauge the experience of fatigue in SLE — revealed greater improvements in physical, mental, and susceptibility to fatigue dimensions in the dapirolizumab pegol group. Specifically, physical fatigue improved by 7.6 points, mental and cognitive fatigue by 5.6 points, and susceptibility to fatigue by 7.8 points (all p < 0.05).
Together, these results suggest dapirolizumab pegol may make a meaningful, real-world difference in the lives of people living with SLE, extending its benefits far beyond disease activity control.
Disease Remission — An Additional Benefit
The study also evaluated dapirolizumab pegol’s ability to enable disease remission — a state where disease activity drops to low or undetectable levels — while reducing reliance on high-dose glucocorticoids, which can contribute to long-term complications and side effects. Disease remission is a major treatment objective for people with SLE and their clinician care teams, reflecting a state where disease-related symptoms diminish or disappear, reducing the likelihood of future complications.
“Being able to address both fatigue and remission are two of the most significant unmet needs in SLE care today, alongside reducing reliance on high-dose glucocorticoids and their related side effects,” said Eric F. Morand, MBBS, Head of the Monash Health Rheumatology Unit in Australia. “In the PHOENYCS GO study, dapirolizumab pegol shows a significant ability to enable low disease activity and remission, offering the possibility for improved disease control while reducing exposure to medications that carry a heavy side effects profile.”
This, combined with its favorable tolerability profile, positions dapirolizumab pegol as a potential breakthrough in the treatment landscape for SLE — delivering additional options for patients and their clinician care teams in a disease area that desperately needs innovation.
Clinical Development
While these results are profoundly encouraging, dapirolizumab pegol’s safety and efficacy remain under investigation. A second Phase 3 trial is currently underway to further validate these results and hopefully enable eventual submission to regulators for approval.
UCB and Biogen are continuing their extensive clinical research program to fully define dapirolizumab pegol’s role in SLE treatment. The companies aim to bring forward a new treatment option for people living with this complex disease — a therapy that not only controls disease activity, but also improves their daily functioning, well-being, and ability to enjoy their lives.
