Dapirolizumab Pegol: A Breakthrough in Lupus Treatment

Dapirolizumab pegol (DZP), a novel Fc-free anti-CD40L drug candidate, has demonstrated significant clinical improvement in disease activity for people living with moderate-to-severe systemic lupus erythematosus (SLE) in the Phase 3 PHOENYCS GO study. The results, presented at ACR Convergence 2024, show that DZP met its primary endpoint, demonstrating statistically and clinically significant improvement across all organ systems as measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA).

The primary endpoint was achieved with a 14.6% higher response rate (49.5%) for participants receiving DZP plus standard of care (SOC) compared to those receiving SOC alone (34.6%). This improvement was associated with meaningful clinical benefit, as a higher BICLA response rate reflects a treatment response across all affected organs at baseline. Additionally, DZP reduced the frequency of severe BILAG flares by 50% through Week 48 compared to SOC alone (11.6% vs. 23.4%).

DZP's positive impact on lupus treatment is further supported by its ability to help patients reduce their corticosteroid use. In the PHOENYCS GO study, 72.4% of participants receiving DZP plus SOC were able to reduce their corticosteroid dose from >7.5 mg/day prednisone equivalent at baseline to ≤7.5 mg/day at Week 48, compared to 52.9% of those receiving SOC alone. This 17.1% increase in corticosteroid tapering indicates that DZP, in combination with SOC, can help patients manage their SLE while minimizing the side effects associated with long-term corticosteroid use.

Moreover, DZP showed promising results in achieving Lupus Low Disease Activity State (LLDAS). A 20.9% greater proportion of participants in the DZP group achieved LLDAS at Week 48 compared to SOC alone (40.9% vs. 19.6%). This significant improvement in LLDAS indicates that DZP may help patients with SLE achieve and maintain lower disease activity, potentially reducing the burden of the disease.



In terms of safety, DZP demonstrated a generally favorable profile. While 82.6% of patients receiving DZP+SOC experienced at least one treatment-emergent adverse event (TEAE), the proportion of patients with serious TEAEs was lower (9.9% vs. 14.8%). Opportunistic infections were reported in 2.8% and 0.9% of patients in the DZP+SOC and PBO+SOC groups, respectively. There was one thromboembolic TEAE (myocardial infarction) and one death (due to gangrene-related sepsis) in patients with predisposing medical history receiving DZP+SOC.

In conclusion, Dapirolizumab pegol has shown great promise in treating moderate-to-severe SLE, demonstrating significant improvement in disease activity across all organ systems and reducing the need for corticosteroid use. With a generally favorable safety profile, DZP offers hope for patients seeking more effective and less invasive treatment options for this chronic and debilitating autoimmune disease. As the clinical development of DZP continues, investors should keep a close eye on this promising drug candidate and its potential impact on the lupus treatment market.