Dapirolizumab Pegol Phase 3 Data: Significant Reduction in Lupus Activity Presented at ACR

BRUSSELS, Belgium and CAMBRIDGE, MA, USA - November 19, 2024 - UCB and Biogen Inc. unveiled the detailed results from their Phase 3 PHOENYCS GO study which evaluated dapirolizumab pegol (DZP), an innovative Fc-free anti-CD40L drug candidate. This study revealed significant clinical improvements in disease activity for individuals with moderate-to-severe systemic lupus erythematosus (SLE). The findings were presented during the ACR Convergence 2024, the American College of Rheumatology’s annual meeting in Washington, DC.

Dr. Megan E.B. Clowse, the study's principal investigator and Associate Professor of Medicine at Duke University School of Medicine, remarked on the critical need for new treatments for SLE patients, highlighting the promise of dapirolizumab pegol. Clowse noted that participants experienced reduced lupus activity and were able to taper off steroids, both crucial for those managing this chronic autoimmune disorder.

The PHOENYCS GO study involved 321 participants who received intravenous doses of DZP every four weeks. The primary endpoint focused on improving moderate-to-severe disease activity, measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) after 48 weeks. Results indicated participants receiving DZP with standard of care (SOC) had a significantly higher response rate (49.5%) compared to those receiving SOC alone (34.6%), with a 14.6% difference (p=0.0110). This higher BICLA response rate suggests a comprehensive treatment response across all affected organs, providing meaningful clinical benefits.

For the first secondary endpoint, BICLA response at Week 24, participants on DZP plus SOC had a 46.6% response rate versus 38.3% for those on SOC alone. However, this did not reach statistical significance. Since the first secondary endpoint did not achieve statistical significance, subsequent secondary endpoint analyses are considered descriptive.

Additional secondary endpoints showed that DZP contributed to clinical improvements. These included measures like the SLE Responder Index (SRI)-4 response, corticosteroid tapering, SLE Disease Activity Index-2K (SLEDAI-2K), achieving Lupus Low Disease Activity State (LLDAS), and preventing severe BILAG flares.

Fiona du Monceau, Head of Patient Evidence at UCB, emphasized the differentiated approach of targeting the CD40L pathway, leading to meaningful improvements across various disease domains. She expressed optimism about the ongoing clinical development of dapirolizumab pegol, particularly its potential impact on women, who are disproportionately affected by lupus.

The safety profile of dapirolizumab pegol appeared generally favorable, consistent with previous studies and SLE patients receiving immunomodulators. A higher proportion of participants on DZP plus SOC reported treatment-emergent adverse events (TEAEs) compared to those on SOC alone (82.6% vs. 75.0%). Serious TEAEs were noted in 9.9% of participants on DZP plus SOC versus 14.8% on SOC alone. Opportunistic infections were slightly more common in the DZP group (2.8%) compared to the SOC group (0.9%). Discontinuation rates due to TEAEs were similar between the two groups.

Dr. Diana Gallagher from Biogen reinforced the company's commitment to developing diverse treatments for lupus to address the varied patient experiences. She highlighted the potential of dapirolizumab pegol to transform SLE care, expressing dedication to advancing this program with UCB.

Participants from the PHOENYCS GO study will continue in a long-term open-label follow-up. UCB and Biogen plan to start a second Phase 3 trial called PHOENYCS FLY in the coming year.

The safety and efficacy of dapirolizumab pegol in treating SLE have not been fully established. It is not yet approved for use in SLE by any regulatory authority globally.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, with symptoms ranging from rashes and arthritis to more severe conditions like nephritis and seizures. Women, particularly those from certain ethnic backgrounds, are more frequently affected by SLE, often experiencing earlier onset and more aggressive disease.

Dapirolizumab pegol is a humanized Fc-free PEG-conjugated antigen-binding fragment that inhibits CD40L signaling, thereby reducing B cell activation and autoantibody production. This drug candidate is currently under Phase 3 clinical development for SLE treatment through a collaboration between UCB and Biogen.

UCB, headquartered in Brussels, Belgium, focuses on innovative treatments for severe diseases of the immune and central nervous systems. Founded in 1978, Biogen, based in Cambridge, MA, USA, is a leading biotechnology company committed to pioneering new medicines for transforming patient lives.