Dapirolizumab pegol, an experimental therapy being developed by UCB and Biogen, has demonstrated statistically and clinically significant improvements in disease activity for individuals with systemic lupus erythematosus (SLE) in a Phase 3 clinical trial. The full results of the PHOENYCS GO trial were presented at the American College of Rheumatology's annual meeting. The study revealed that patients treated with dapirolizumab pegol experienced 50% fewer severe disease flares compared to those receiving standard of care and placebo.
Targeting CD40L in SLE
Dapirolizumab pegol is designed to inhibit CD40L signaling, a key molecular pathway involved in the activation of immune cells that drive the autoimmune response characteristic of lupus. By blocking this pathway, the drug aims to modulate the immune system and reduce the severity of SLE symptoms.
Fiona du Monceau, head of patient evidence at UCB, emphasized the challenges in treating lupus due to the variability in symptoms and severity among patients, noting the disproportionate impact on women. "With dapirolizumab pegol, we believe that our differentiated approach that targets the CD40L pathway results in clinically meaningful improvements across multiple disease domains and could substantially impact the burden of this disease in particular for women," said du Monceau.
PHOENYCS GO Trial Details and Results
The PHOENYCS GO trial (NCT04294667) enrolled 321 participants with SLE, randomly assigning them to receive either dapirolizumab pegol or a placebo intravenously every four months for 48 weeks, in addition to their standard of care treatments. The primary endpoint was the proportion of patients achieving a response on the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at week 48, indicating a reduction in lupus disease activity. The trial met this endpoint, with 49.5% of patients on dapirolizumab pegol achieving a BICLA response compared to 34.6% on placebo.
Other measures of disease activity, including the SLE Responder Index (SRI)-4 response, the Lupus Low Disease Activity State (LLDAS), and the SLE Disease Activity Index-2K (SLEDAI-2K), also showed significant differences favoring dapirolizumab pegol over placebo at 48 weeks.
Clinical Impact and Safety Profile
Over the 48-week study period, patients receiving dapirolizumab pegol experienced approximately 50% fewer severe disease flares (11.6% vs. 23.4%). Furthermore, a significantly higher proportion of patients on dapirolizumab pegol (72.4% vs. 52.9%) were able to reduce their corticosteroid dosage to 7.5 mg/day or less at week 48. This is particularly important, as long-term corticosteroid use is associated with significant side effects.
Megan E.B. Clowse, MD, principal investigator of the study and a professor at the Duke University School of Medicine, stated that "there remains a significant unmet need for additional treatment options" for SLE patients. "The results we observed in PHOENYCS GO suggest dapirolizumab pegol has the potential to be impactful for this chronic and debilitating autoimmune disease," Clowse added. "Across clinical endpoints we observed a positive effect."
While the rate of treatment-emergent adverse events was slightly higher in the dapirolizumab pegol group (82.6% vs. 75%), the rate of serious treatment-emergent adverse events was lower (9.9% vs. 14.8%). The percentage of patients who discontinued treatment due to safety issues was similar between the two groups (4.7% vs. 3.7%). Opportunistic infections were reported in 2.8% of participants receiving dapirolizumab pegol and in 0.9% of those receiving placebo. Overall, dapirolizumab pegol was generally well tolerated.
Future Directions
UCB and Biogen are moving forward with the clinical development of dapirolizumab pegol in a second Phase 3 study, PHOENYCS FLY (NCT06617325). This trial will further evaluate the efficacy and safety of dapirolizumab pegol compared to placebo in patients with moderate to severe SLE.
