UCB  and Biogen Inc.announced that The Lancet, a world-leading medical journal, has published the full results from the Phase 3 PHOENYCS GO clinical trial evaluating dapirolizumab pegol (DZP), an investigational, novel Fc-free CD40L inhibitor, in patients living with moderate-to-severe active systemic lupus erythematosus (SLE). The results showed statistically significant improvement in disease activity with DZP added to standard of care (SOC) versus placebo plus standard of care.

“The publication of the PHOENYCS GO results in The Lancet reflects the importance of these data to the rheumatology community, providing evidence of dapirolizumab pegol as a potential treatment option for people living with systemic lupus erythematosus,” said Megan E. B. Clowse, M.D., MPH, Chief of the Division of Rheumatology and Immunology, Duke University, and primary author of the publication. “Given the acute need for additional treatment options for SLE, these findings are encouraging for both clinicians and patients and clearly warrant further evaluation in the confirmatory Phase 3 PHOENYCS FLY study.”

In the Phase 3 study, DZP successfully met the primary endpoint: a significantly greater proportion of patients receiving DZP plus standard of care (SOC) achieved British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response at Week 48 (50%; 103/208) compared to placebo plus SOC (35%; 37/107; p=0.011).¹ BICLA is a composite endpoint measuring clinically relevant improvement of disease activity across all affected organ systems with no worsening in other lupus domains; a higher BICLA response rate reflects a treatment response and is associated with clinical benefit.

Because the first key secondary endpoint was not met (BICLA response at week 24), subsequent outcomes were not controlled for multiplicity. Results in favor of DZP plus SOC were observed across multiple outcomes, including severe BILAG flares, SRI-4, SLEDAI-2K, skin- and joint-related outcomes, and the serological markers anti-dsDNA antibodies and complement C3 and C4.¹ Additionally, at week 48 the data showed clinically meaningful improvements in patient-reported FACIT-Fatigue, which is often cited by patients as one of the most debilitating symptoms of SLE.^1,2 Importantly, these results were achieved within the context of glucocorticoid tapering in line with treatment guidelines.^1,3 At week 48, a greater proportion of patients in the DZP plus SOC group versus PBO plus SOC were able to reduce their glucocorticoid dose from >7.5 mg/day to ≤7.5 mg/day, suggesting a glucocorticoid-sparing effect of DZP.¹

In the PHOENYCS GO study, DZP demonstrated a generally favorable safety profile, with safety findings consistent with previous DZP studies.^1,4 Treatment-emergent adverse events (TEAEs) were more common with DZP plus SOC versus PBO plus SOC (82.6% [176/213] vs. 75.0% [81/108], respectively), while serious TEAEs were less frequent in the DZP plus SOC arm (10.0% [21/213] vs. 14.8% [16/108]) respectively.¹ Discontinuations due to TEAEs were low in both groups (4.7% vs. 3.7%) respectively.¹

These positive Phase 3 results support the continued development of DZP. UCB and Biogen are actively progressing the confirmatory Phase 3 PHOENYCS FLY clinical trial (NCT06617325), which is currently recruiting patients and is intended to support future regulatory filings.⁵

Further data from the PHOENYCS GO study will be presented this week at the Annual European Congress of Rheumatology (EULAR).