Eric F. Morand, MBBS
Credit: Monash University
Dapirolizumab pegol (DZP) improved disease activity and fatigue in people with moderate-to-severe systemic lupus erythematosus (SLE), in new data from the phase 3 PHOENYCS GO trial.
These new data were presented at last month’s European Alliance of Associations for Rheumatology (EULAR) Congress 2025 held in Barcelona, Spain, by Eric F. Morand, MBBS, Head of the Monash Health Rheumatology Unit, Monash University, Australia.
Morand and colleagues found that at Week 48, 40.9% of participants receiving DZP plus standard of care (SOC) achieved low disease activity, more than double the rate in the SOC-only group (19.6%; nominal* P <.0001). As early as Week 12, significantly more participants on DZP plus SOC achieved low lupus disease activity state (LLDAS) versus SOC alone (nominal* P <.05). Additionally, 23.6% of the DZP group maintained low disease activity in ≥50% of visits over 48 weeks, compared to 15.9% with SOC alone (nominal* P = .1042). At Week 48, 19.2% of participants receiving DZP achieved remission (DORIS criteria), compared to 8.4% in the SOC-only group (nominal* P = .0056).
HCPLive spoke with Morand to learn more about the findings and DZP’s potential in treating SLE. He also discussed the therapeutic potential of CD40L inhibition and the importance of minimizing glucocorticoid exposure.
HCPLive: With improvements in BICLA, disease activity, fatigue and others, from your perspective, what are the most meaningful findings and outcomes seen with DZP from PHOENYCS GO?
Morand: The BICLA and fatigue results are both equally exciting. BICLA is a validated way to measure response to therapy in an SLE trial and has been used to support the registration of anifrolumab – so these results are very supportive for the potential for DZP to be registered in the future. The Fatigue results are different – these symptoms are incredibly important to patients but have been very hard to impact on in the past…the potential to hit on disease activity AND fatigue with one therapy is really going to be welcomed by patients.
Can you discuss the significance of the LLDAS and DORIS remission endpoints in the context of SLE management today? How do you interpret the magnitude of benefit seen in these measures?
Attainment of treat to target goals is now enshrined in both the EULAR and ACR guidelines as the goal of treatment because these endpoints have been shown in study after study to be associated with improved long term outcomes including disease activity, flare, damage accrual, quality of life and even mortality. I think the gold standard for a modern lupus therapy should be to show that it safely increases attainment of these end points vs the comparator. In this EULAR abstract we can see very meaningful separation from placebo very soon after starting treatment with DZP, and strong and significant separation across time all the way to last visit.
Trials in lupus are hard, so we are left needing to interpret results that can only be reported with nominal significance. The LLDAS and remission analysis reported at EULAR were pre-specified analyses, not post hoc, so I think we can be pretty confident in them.
LLDAS and DORIS achievement requires tapering to low doses of glucocorticoids. Can you discuss why this is important for long-term SLE management?
The reason that glucocorticoid ceilings are included in both LLDAS and DORIS remission is that glucocorticoid use contributes in a dose-dependent way to net harm to patient including via damage accrual. Again, current guidelines stress minimizing glucocorticoid exposure and attainment of LLDAS and DORIS are validated metrics to ensure this is achieved while disease control is maintained.
What do these data tell us about the therapeutic potential of CD40L inhibition in SLE?
It is a positive phase 3 trial – evidence does not get much better than this. Trials in SLE are really hard to do, as the disease is heterogenous and endpoints disfavor success – this means a positive result has basically happened against the odds and is meaningful. How DZP fits into the treatment paradigm remains to be seen as the pipeline has lots of other interesting medicines in development which together will change the landscape very greatly in the next handful of years. Regardless, these data strongly suggest that CD40L has a real place in our care paradigm.
In your opinion, what gaps in current SLE care could DZP meaningfully address if approved and how could it potentially shift the treatment landscape?
Our current biologicals achieve LLDAS in only 30% of patients after one year, and remission in around half that – so it is clear there is a lot of room for improvement with the option of additional therapies to try. It isn’t currently possible to say one biologic is ‘better’ than another, but as we get used to the patient profiles that may respond differently to differently targeted medicines, or differences in safety profile that may influence our choice based on patients’ comorbidities, things will get clearer. On the basis that DZP clearly increases attainment of treatment goals, it will have a significant role if it gains regulatory approval.
Transcript has been edited for clarity.