UCB and Biogen have announced positive topline results from the Phase 3 PHOENYCS GO study, revealing that dapirolizumab pegol, an investigational drug, met its primary endpoint in treating moderate-to-severe systemic lupus erythematosus (SLE). The trial's success marks a significant step forward in addressing the unmet needs of SLE patients, particularly women, who are disproportionately affected by this chronic autoimmune disease.
The PHOENYCS GO study (NCT04294667) was a multicenter, randomized, double-blind, placebo-controlled trial involving 321 patients. Participants received dapirolizumab pegol in addition to standard of care (SOC). The primary endpoint was defined as the improvement of moderate-to-severe disease activity, measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at week 48.
The study demonstrated that dapirolizumab pegol, when added to SOC, resulted in a statistically significant improvement in disease activity compared to placebo plus SOC. Furthermore, the drug showed clinical improvements in key secondary endpoints, including measures of disease activity and the frequency of flares. The safety profile of dapirolizumab pegol was consistent with previous studies, aligning with expectations for SLE patients receiving immunomodulatory treatment.
Targeting the CD40L Pathway
Dapirolizumab pegol is a humanized anti-CD40L antibody fragment that inhibits the interaction between CD40L and CD40. This interaction is crucial in T cell activation and B cell antibody production, key drivers of SLE pathogenesis. By blocking this pathway, dapirolizumab pegol aims to reduce B cell activation and autoantibody production, mitigating the inflammatory processes characteristic of SLE.
Diana Gallagher, MD, Head of AD, MS and Immunology Development Units at Biogen, stated, "Our hypothesis is that impacting the CD40L pathway, a central mechanism in immune response, would translate to significant impact on SLE disease burden. These results demonstrate that dapirolizumab pegol has the promise to provide meaningful benefit in this serious, chronic, and often devastating disease."
Next Steps: PHOENYCS FLY and Further Data Presentation
Building on the success of the PHOENYCS GO study, UCB and Biogen plan to initiate a second Phase 3 trial, PHOENYCS FLY, later this year. Patients from the PHOENYCS GO study will continue to be monitored in a long-term, open-label extension study. Detailed results from the PHOENYCS GO study are slated for presentation at an upcoming medical congress.
Fiona du Monceau, Head of Patient Evidence at UCB, commented, "These positive results with dapirolizumab pegol represent encouraging progress in the development of medicines that can improve the lives of those living with lupus, an area that remains one of high unmet medical need and where women are disproportionately affected."
Current SLE Treatment Landscape
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organ systems. Current treatments include antimalarials, corticosteroids, immunosuppressants, and biologics such as belimumab and anifrolumab. Despite these options, many patients still experience uncontrolled disease activity and flares, highlighting the need for new therapeutic approaches.
The potential approval of dapirolizumab pegol could provide a valuable addition to the SLE treatment armamentarium, offering a novel mechanism of action to address the complex immune dysregulation underlying the disease.
