UCB and Biogen report higher TRM-SLE response rates and sustained disease control with dapirolizumab pegol in Phase 3 lupus analyses at ACR 2026.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
UCB and Biogen reported new clinical data on November 9, 2026, showing higher treatment response rates with investigational dapirolizumab pegol (DZP) in patients with systemic lupus erythematosus (SLE). Presented across five posters at ACR Convergence 2026 in Orlando, Florida, the findings included a post-hoc application of the novel Treatment Response Measure for SLE (TRM-SLE) to the Phase 3 PHOENYCS GO trial and a separate analysis of sustained low disease activity and remission.
Dapirolizumab Pegol and Its Mechanism
DZP is an investigational, humanized, Fc-free, polyethylene glycol (PEG)-conjugated antigen-binding fragment (Fab’) that inhibits CD40 ligand (CD40L) signaling. CD40L inhibition is intended to modulate immune pathways involved in SLE pathogenesis, including interactions between T cells, B cells and antigen-presenting cells. The candidate is being developed through a collaboration between UCB and Biogen.
DZP remains investigational, with its safety and efficacy not established for regulatory approval. It is not approved by any health authority worldwide.
TRM-SLE: A Novel Approach to Measuring Treatment Response
TRM-SLE is a clinical outcome assessment developed by a global taskforce led by Monash University, involving clinicians, patients, industry partners and regulatory experts. It evaluates clinically meaningful improvements across six organ domains: arthritis, mucocutaneous involvement, nephropathy, serositis, hemolytic anemia and thrombocytopenia.
TRM-SLE-50 represents clinically meaningful improvement in at least half of a patient’s active organ domains, while TRM-SLE-100 requires improvement across all active domains. The measure aims to capture organ-specific improvements that conventional composite measures may not fully reflect.
PHOENYCS GO Trial: Primary Efficacy Findings
PHOENYCS GO (NCT04294667) was a randomized, double-blind, placebo-controlled Phase 3 trial evaluating intravenous DZP (24 mg/kg every four weeks) plus standard of care (SOC) against placebo plus SOC over 48 weeks. The study randomized 321 patients across 177 centres in 25 countries. Six patients were excluded from the efficacy analysis following a Good Clinical Practice compliance issue at one study site, leaving 315 patients in the full-analysis set.
The primary endpoint, BICLA response at Week 48, was achieved by 50% (103/208) of patients receiving DZP plus SOC compared with 35% (37/107) receiving placebo plus SOC (p=0.011). The treatment difference was 14.6 percentage points (95% CI 3.3–25.8). SRI-4 response, a secondary outcome not controlled for multiplicity, was 60% versus 41%.
TRM-SLE response (Poster 1296)
Through Week 48, TRM-SLE-50 was achieved by 61.2% of patients receiving DZP plus SOC versus 43.2% receiving placebo plus SOC. TRM-SLE-100 rates were 52.5% and 36.8%, respectively. Nine patients with baseline serositis were excluded because the patient numerical rating scale required for this domain was not collected in PHOENYCS GO, leaving 202 and 104 patients in the respective analyses.
Baseline disease activity predominantly involved arthritis and mucocutaneous domains. The findings therefore provide greater insight into joint and skin responses than into less represented organ manifestations.
Sustained low disease activity and remission (Poster 2196)
A separate post-hoc analysis assessed sustained attainment at each of the final three study visits (Weeks 40, 44 and 48). Results favoured DZP across all three measures:
- Sustained LLDAS: 24.0% (50/208) versus 10.3% (11/107); nominal p=0.0012.
- Sustained LLDAS-5: 19.2% (40/208) versus 5.6% (6/107); nominal p=0.0002. This measure requires a glucocorticoid dose of 5 mg/day prednisone equivalent or less.
- Sustained DORIS remission: 11.5% (24/208) versus 4.7% (5/107); nominal p=0.0253.
The trial protocol also required glucocorticoid tapering to begin by Week 8 in patients receiving more than 7.5 mg/day prednisone equivalent, targeting a dose of 7.5 mg/day or less.
Safety Profile
In the published PHOENYCS GO trial, treatment-emergent adverse events occurred in 83% of patients receiving DZP versus 75% receiving placebo. Serious treatment-emergent adverse events occurred in 10% versus 15%, respectively. Serious infections were reported in 4% and 6%, while infusion-related hypersensitivity reactions occurred in 3% of DZP-treated patients. One myocardial infarction and one death associated with gangrene-related sepsis were reported in the DZP group.
Clinical Interpretation
The new analyses extend the efficacy findings from PHOENYCS GO by examining treatment response across individual organ domains and the sustained attainment of low disease activity and remission. The 18-percentage-point difference in TRM-SLE-50 and higher sustained LLDAS rates suggest that DZP may provide benefits across complementary measures of disease control.
However, these findings require cautious interpretation. Both ACR analyses were post-hoc, and the reported p-values for LLDAS and remission were nominal, without adjustment for multiple comparisons. No p-values or confidence intervals were reported for the TRM-SLE comparisons. Furthermore, TRM-SLE requires additional validation before it can be considered an established clinical trial endpoint.
The relatively low sustained remission rates and limited representation of organ domains such as nephropathy also restrict broader conclusions. The findings support further investigation of DZP and the potential utility of TRM-SLE, but do not establish long-term efficacy or safety beyond the 48-week study period.
References
ACR 2026: Dapirolizumab Pegol Associated with Greater Treatment Response Rates Versus Placebo in SLE Using Novel Treatment Response Measure, Biogen, 09 November 2026
Clowse M, Isenberg D, Merrill J et al., Efficacy and safety of the CD40 ligand inhibitor dapirolizumab pegol in systemic lupus erythematosus (PHOENYCS GO): a randomised, double-blind, placebo-controlled, phase 3 trial, The Lancet, 2026; 407, 2291-2304, https://doi.org/10.1016/S0140-6736(26)00691-4
A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants with Moderately to Severely Active Systemic Lupus Erythematosus (PHOENYCS GO), ClinicalTrials.gov ID NCT04294667
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.