Translational medicine expert at the University of Leeds

Ed Vital, MD

Ianalumab Provides Clinical Benefit in Lupus Phase 2 Trial, With Ed Vital, MD

 in Chicago, Ed Vital, MD, a translational medicine expert at the University of Leeds, discussed new phase 2 findings showing that ianalumab (VAY736

, a next-generation B–cell–targeting antibody, achieved sustained 

 disease control and supported steroid tapering over 1 year.

Ianalumab is a fully human monoclonal antibody targeting the BAFF receptor, designed to overcome limitations of earlier B cell therapies such as rituximab.

“Ianalumab is a really interesting drug,” Vital said. “Ianalumab is a drug that targets B cells. Now, B cells as a target are not new. In fact, it's [been] about 20 years that we've started targeting them for depletion using rituximab, something I've worked on throughout my career, and one of the things I showed a long time ago is that the reason why rituximab doesn't work well enough for all patients is because it doesn't kill B cells completely—it reduces their number. We used to think they've all gone then we discovered that there are niches where they're hiding, and that's where the disease persists and comes back. So that's led to interest in developing…B cell depleting drugs that are more efficient.”

Vital explained that ianalumab has a dual mechanism of action, both B cell depletion and BAFF pathway blockade, which may account for its stronger and more durable effects.

Unlike rituximab’s lengthy infusions, ianalumab is given subcutaneously once a month and includes afucosylation, a structural modification that enhances antibody-dependent cell killing.

In a phase 2a randomized trial, 67 patients with active systemic lupus erythematosus (SLE) were randomized 1:1 to receive ianalumab 300 mg (n = 34) or to receive placebo (n = 33) and then ianalumab in the open-label phase. The study found that ianalumab 300 mg administered every 4 weeks produced notable efficacy over 52 weeks.

At week 52, 38.2% of patients on continuous ianalumab achieved Lupus Low Disease Activity State (LLDAS) and 26.5%

 compared with 21.2% and 12.1%, respectively, among those who began on placebo. Median time to first LLDAS was 40 weeks for the ianalumab arm.

The trial included a protocolized glucocorticoid taper, with 85.3% of patients on continuous ianalumab reducing their steroid dose to ≤5 mg after 52 weeks, compared with 72.7% of those switching from placebo. Patients on continuous ianalumab also spent a greater cumulative proportion of time in low disease activity, remission, and on lower steroid doses.

“Longer exposure to treatment led to not just response but…cumulative benefit of more time on target, and that starts to kick in the longer you spend on [the] drug,” Vital said. “This is a small study, and it's only a year duration, or just over a year, but [I] predict that bigger studies that had long-term extensions would translate into prevention of damage [and] better quality of life.”

Vital has no relevant reported disclosures.

Morand E, Gaillez C, Oliver S, Ghanshani S, Pozzobon M, Bao W, Vital E. Achieving Sustained Lupus Low Disease Activity State and Remission With Ianalumab (VAY736) in Patients with Systemic Lupus Erythematosus: A post hoc Analysis From a Phase II Study [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). 

https://acrabstracts.org/abstract/achieving-sustained-lupus-low-disease-activity-state-and-remission-with-ianalumab-vay736-in-patients-with-systemic-lupus-erythematosus-a-post-hoc-analysis-from-a-phase-ii-study/.

Cuker A, Hanny Al-Samkari, Barcellini W, et al. Ianalumab, a Novel Anti-B-Cell Activating Factor (BAFF) Receptor (BAFF-R) Monoclonal Antibody (mAb) in Development for Immune Thrombocytopenia (ITP) and Warm Autoimmune Hemolytic Anemia (wAIHA), Has Demonstrated a Favorable Safety Profile in Sjögren’s Syndrome (SjS), Systemic Lupus Erythematosus (SLE) and Chronic Lymphocytic Leukemia (CLL). Blood. 2023;142(Supplement 1):5427-5427. 

doi:https://doi.org/10.1182/blood-2023-180055

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Phase 2 trial shows ianalumab achieves sustained lupus disease control, supports steroid tapering, and increases time in remission over 1 year.

What’s Next for Dapirolizumab Pegol Following Lupus Phase 3 Trial, With Ed Vital, MD

Pivotal data from the phase 3 PHOENYCS GO trial

 showed dapirolizumab pegol (DZP) significantly stabilized disease activity and improved remission in patients with 

Investigator Ed Vital, MD, a translational medicine expert at the University of Leeds, presented this data on Sunday, October 26 at 

 sat with Vital during the meeting to discuss the significance of these findings, how DZP may impact lupus care, and what is next for DZP in the future.

“The really big next step is the second phase 3 trial,” Vital said. “Second [trial] is in progress now, which has a very similar design.”

Aside from the second phase 3 trial, investigators plan to assess patient-reported outcomes with DZP.

“Those can be quite difficult to demonstrate in lupus trials,” he said. “We think these drugs don't just improve physician assessments, but also make people feel better, but that that can be quite hard to show in trials…some of the early analyses of these trials, not all of it published yet, does seem to report quite good outcomes in things like patients’ report of how their fatigue improved. There'll be [a lot] to chew over with the data from these trials over the next few years.”

In this current phase 3 study, a 48-week, randomized, double-blind, placebo-controlled design, Vital and colleagues evaluated DZP in patients aged ≥ 16 years with moderate-to-severe SLE on stable standard-of-care, either antimalarials, glucocorticoids, or immunosuppressants. Participants were randomized 2:1 to receive DZP plus standard-of-care or placebo plus standard-of-care every 4 weeks.

The primary endpoint showed a greater rate of BILAG-based Composite Lupus Assessment (BICLA) response with DZP versus placebo. The study also evaluated remission using the DORIS criteria and low disease activity through the Lupus Low Disease Activity State (LLDAS), with encouraging results: 40.9% of patients on DZP achieved LLDAS at week 48 versus 19.6% with placebo (

 < .0001), and 19.2% reached DORIS-defined remission versus 8.4% with placebo (

 = .0056). Additionally, patients on DZP spent more time in LLDAS (2.9 vs 1.8 visits; 

 = .0016) and more often maintained LLDAS across visits through week 48.

At the meeting, Vital also presented a post-hoc analysis from a phase 2 study, which showed that lanalumab achieved lupus sustained low activity state and remission in patients with systemic lupus erythematosus.

“In the world of lupus, we've spent a long time with only one biologic,” Vital said. “Now we have two biologics, one other novel therapy, but there are lots of phase 3 trials in progress, and in the next 2 to 3 years, we could be in a situation where there are a lot of drugs produced, which, in some ways, will make things a little bit more complicated. All these drugs work in different ways, so rheumatologists are going to have to think, ‘Well, do I want to target B cells, which I want to target interferon, which I want to target CD40, or do I want to target TLS-7, and so on. I predict there'll be intense interest in trying to work out which mechanism is right for which patient, which is difficult, but it's a good problem to have.”

Morand E, Carter L, Dall'Era M, Petri M, Vital E, Jimenez T, Gaiha-Rohrbach J, Lauwerys B, Nelde A, Stach C, van Vollenhoven R. Achievement of Low Disease Activity and Remission in Patients with Systemic Lupus Erythematosus Treated with Dapirolizumab Pegol: 48-Week Results from a Phase 3 Trial [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). 

https://acrabstracts.org/abstract/achievement-of-low-disease-activity-and-remission-in-patients-with-systemic-lupus-erythematosus-treated-with-dapirolizumab-pegol-48-week-results-from-a-phase-3-trial/

https://acrabstracts.org/abstract/achieving-sustained-lupus-low-disease-activity-state-and-remission-with-ianalumab-vay736-in-patients-with-systemic-lupus-erythematosus-a-post-hoc-analysis-from-a-phase-ii-study/

Phase 3 data show dapirolizumab pegol improved remission and disease stability in lupus; a second trial and patient-reported outcomes are now underway.

Dapirolizumab Pegol Shows Promise in Lupus During Phase 3 Trial, With Ed Vital, MD

spoke with Ed Vital, MD, a translational medicine expert at the University of Leeds, about the latest findings from the phase 3 PHOENYCS GO trial of dapirolizumab pegol (DZP) in 

 DZP is a novel CD40 ligand inhibitor that modulates B cell activation and broader immune pathways, offering a distinct mechanism compared with existing therapies.

“The is a new biologic for lupus that works in a different way from the drugs that we have already,” Vital told HCPLive. “It targets the interaction of a molecule called CD 40 and CD 40 ligand, and that's a target that's been of interest for a while, because we know it has a really important role in B cell activation, which is important in diseases like lupus, but we now recognize actually that CD 40 ligand interactions is involved in many different functions in the immune systems.”

These findings, presented at ACR 2025 in Chicago from October 24 – 29, 2025, suggest that DZP not only improves response rates but also supports sustained low disease activity and remission, underscoring its potential as a meaningful addition to the SLE treatment landscape.

PHOENYCS GO trial, a 48-week, randomized, double-blind, placebo-controlled study, evaluated DZP in patients aged ≥ 16 years with moderate-to-severe, active SLE despite stable standard-of-care therapy (antimalarials, glucocorticoids, and immunosuppressants).

 Patients were randomized 2:1 to receive DZP plus standard-of-care (SOC) or placebo plus SOC every 4 weeks. The primary endpoint, previously reported, showed a greater rate of BILAG-based Composite Lupus Assessment (BICLA) response with DZP versus placebo.

Vital highlighted that beyond overall response, the study assessed remission per the DORIS definition and low disease activity per the Lupus Low Disease Activity State (LLDAS). Results were encouraging: 40.9% of patients receiving DZP+SOC achieved LLDAS at week 48 versus 19.6% with placebo (

 <.0001), and 23.6% of DZP-treated patients maintained LLDAS in at least half of their visits through week 48 versus 15.9% for placebo. The cumulative number of visits in LLDAS was also greater for DZP (2.9 vs 1.8;

 =.0016). Achievement of DORIS was similarly improved, with 19.2% of DZP patients reaching remission at week 48 versus 8.4% with placebo (

 =.0056); a greater proportion of patients on DZP vs placebo reached remission at weeks 20, 32, and 36 (

Vital highlighted the difficulty of measuring flares in lupus, a disease marked by fluctuating activity. The trial used innovative flare definitions that tracked sequential disease activity over time rather than relying on isolated snapshots. This approach showed more flares in the placebo group and demonstrated that DZP stabilized disease activity, improving sustained low disease activity and remission rates. Vital explained that the analysis tested new ways to define moderate flares, allowing a more accurate understanding of DZP’s effects by capturing disease changes occurring at different times as part of a single flare event rather than single snapshots.

“What we said is, let's just look at flares that if they evolved over not 1 time point, but over 2,” Vital said. “When you do that, what happens is the number of flares you detect goes up. You find more, but you find a lot more on the placebo arm, and you don't see many more in the deeper realism map arm. In other words, the difference between the two treatments got greater and greater when we made this broader [flare] definition."

Morand E, Carter L, Dall'Era M, Petri M, Vital E, Jimenez T, Gaiha-Rohrbach J, Lauwerys B, Nelde A, Stach C, van Vollenhoven R. Achievement of Low Disease Activity and Remission in Patients with Systemic Lupus Erythematosus Treated with Dapirolizumab Pegol: 48-Week Results from a Phase 3 Trial [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/achievement-of-low-disease-activity-and-remission-in-patients-with-systemic-lupus-erythematosus-treated-with-dapirolizumab-pegol-48-week-results-from-a-phase-3-trial/. Accessed November 3, 2025.

Cutcutache I, Powlesland A, Skelton A, Sun Y, Page M, Stojan G, Lipsky P, Skowera A, Stach C. Dapirolizumab Pegol Impacts Important Immunologic Pathways in SLE: Pharmacodynamic Analysis of B Cell and Type I Interferon Pathways from a Phase 2b Trial [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/dapirolizumab-pegol-impacts-important-immunologic-pathways-in-sle-pharmacodynamic-analysis-of-b-cell-and-type-i-interferon-pathways-from-a-phase-2b-trial/. Accessed November 4, 2025.

At ACR 2025, Vital discussed phase 3 data showing dapirolizumab pegol improved remission and stabilized disease activity in patients with lupus.

Ed Vital, MD

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