Novel CD40L inhibitor excels in reaching lupus goal of care

Adding the novel CD40L inhibitor dapirolizumab pegol (DZP) to standard of care appears to help patients with systemic lupus erythematosus (SLE) achieve low disease activity and remission, according to a prespecified secondary outcome analysis of the phase III PHOENYCS GO trial.

At week 48, 40.9 percent of patients treated with DZP were in low disease activity as compared with 19.6 percent of patients treated with placebo (p<0.0001), with treatment given in addition to standard of care in both cases, reported lead researcher Dr Eric Morand from the Monash University, Centre for Inflammatory Diseases, Melbourne, Australia. [EULAR 2025, abstract OP0201]

Morand noted that patients in the DZP group not only achieved more individual visits in low disease activity but were also more likely to sustain this state across multiple visits.

Low disease activity was achieved in at least 50 percent of visits in 23.6 percent of DZP-treated patients vs 15.9 percent of placebo recipients. Furthermore, 38.5 percent vs 22.4 percent met the goal of at least three consecutive visits in low disease activity (p=0.0023), while 28.4 percent vs 16.8 percent met the higher threshold of at least four consecutive visits in this state (p=0.0171).

Finally, 19.2 percent of patients in the DZP group achieved remission as opposed to only 8.4 percent of those in the placebo group (p=0.0056).

Goal of care

Results for the primary endpoint of the PHOENYCS GO, which was presented last year at a separate conference, already demonstrated the beneficial effect of DZP in SLE patients, with 49.5 percent of patients achieving a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 48 compared with 34.6 percent in the placebo group. [ACR Convergence 2024, abstract L16]

“However, EULAR treatment guidelines do not specify the goal of care as attaining a BICLA response. Instead, they specify the goal of care as attaining remission or low disease activity,” Morand said.

“Low disease activity and remission are associated with improved long-term outcomes, including reduced organ damage, reduced flares, improved quality of life, and improved survival,” he said. “And [in PHOENYCS GO], we show that DZP plus standard of care resulted in higher rates of attainment of these goals than placebo plus standard of care.” [Rheumatol Ther 2023;10:1459-1477; Lupus Sci Med 2018;5:e000234]

Overall, this secondary outcome analysis provides further insights into the potential benefits of treatment with DZP for patients with SLE, according to Morand.

PHOENYCS GO

A total of 315 patients with moderate-to-severe active SLE (time since diagnosis, 10 years) were randomly assigned to receive intravenous treatment with either DZP 24 mg/kg (n=208) or placebo (n=107) every 4 weeks, alongside their standard-of-care medication, for 48 weeks. Corticosteroids were tapered.

The mean patient age was 43.5 years in the DZP group and 41.5 years in the placebo group, and 93 percent of the patients overall were female. Around 80 percent of patients in both groups used systemic glucocorticoids concomitantly.

Low disease activity and remission were assessed at every treatment visit. Low disease activity was defined using Low Lupus Disease Activity State (LLDAS), based on a SLE Disease Activity Index-2K (SLEDAI-2K) score ≤4 with no new or worsening activity as scored on the index; a Physician's Global Assessment (PGA) score ≤33; and prednisone-equivalent steroid doses ≤7.5 mg/day for more than half of the last 28 days, as well as for the 7 days before a visit, during the visit, and the following day. LLDAS also required that patients had stable standard maintenance doses of immunosuppressive drugs.

For remission, the DORIS* definition was used: SLEDAI-2K score of 0, PGA ≤16, and prednisone-equivalent doses of ≤5 mg/day for >50 percent of the preceding 28 days and for the 7 days before a visit, during the visit, and the following day.