Transforming autoimmune disease therapy: Perspectives to look forward at EULAR 2025
The 2025 European Alliance of Associations for Rheumatology (EULAR) congress continues the momentum from American College of Rheumatology (ACR) 2024 congress, highlighting innovative advances in therapies for autoimmune diseases. Among these diseases, systemic lupus erythematosus (SLE) and lupus nephritis (LN) remain a key area of focus in research and drug development due to their complex and heterogeneous nature. EULAR 2025 will encompass updates on advances in Chimeric Antigen Receptor T cell therapies (CAR-T), antibody therapies, and a potential revision of EULAR treatment guidelines.
CAR-T therapy: next generation therapies
At EULAR 2025, innovative therapies and data to be presented by companies such as Fate Therapeutics, Cabaletta Bio, and AstraZeneca reveal a shifting field that is exploring durable immune-reset strategies, rather than immune suppression, especially for patients with severe, recurring lupus. However, challenges around CAR-T cost, accessibility, and scalability, as well as the need to expand CAR-T targets and improved safety remain.
Gracell Biotechnologies (a subsidiary of AstraZeneca) will present preliminary results from the first-in-human clinical trial of GC012F (AZD0120), a CD19/BCMA dual-targeting CAR-T cell therapy, in patients with refractory SLE (rSLE). GC012F targets both B cell populations and long-lived plasma cells, the main origins of autoantibodies in SLE. In early Phase 1 data, all 10 enrolled patients had a favorable safety profile with mostly mild immune reactions (low CRS), and no dosing limit toxicities or neurotoxicity (ICANS). By 9 months, 9 of 10 patients met DORIS remission (Definition Of Remission in SLE) – a stringent benchmark in the Treat-to-Target strategy for lupus – evidencing advanced and efficient disease control. GC012F is manufactured using Gracell Biotechnologies’ FasTCAR technology, a next-day CAR-T production platform that was developed to reduce treatment delays and improve cell quality. Traditional CAR-T manufacturing needs sequential steps consisting of T-cell activation, viral transduction, and ex-vivo expansion, which is a labor-intensive process that may take up to 6 weeks. However, the FastCAR platform combines the first two steps into a single “concurrent activation-transduction” step using high-efficiency XLenti vectors which produces T-cells that are directly administered to patients without the need for expansion due to their high proliferative potential. A phase 1/2 study (NCT06530849) is ongoing to further evaluate the safety and efficacy of GC012F.
EULAR 2025 will also highlight Fate Therapeutics’ first-in-class, off-the-shelf induced pluripotent stem cell (iPSC) based CAR-T therapy. Fate will present promising preliminary results on FT819, iPSC-based CD-19 targeted CAR-T cell therapy for patients with moderate-to-severe SLE (NCT06308978). FT819 is an allogenic therapy composed of CD8αβ+ T cells with a memory phenotype and enhanced tissue trafficking which allows for rapid, and sustained B-cell depletion while supporting immune reset. This allogenic therapy addresses limitations of current autologous CAR-T therapies such as lengthy manufacturing, high cost, and hospitalization needs.
Excitement around CAR-T therapies remains high, but early clinical results have yet to consistently replicate the dramatic outcomes initially reported by Professor Georg Schett (Friedrich-Alexander University of Erlangen-Nuremberg), and manufacturing limitations continue to affect affordability and scalability. Innovations such as dual-targeting and off-the-shelf platforms are slowly addressing these issues. As the field progresses, clearer long-term safety data and standardized remission criteria for CAR-T treatment will be essential. For now, CAR-Ts remain best suited for severe, refractory cases, but their potential for durable, drug-free remission may reshape the future treatment paradigm.
Antibody-based therapies: refining the approach
Currently, antibody-based treatments options used concomitantly with background therapy (e.g. hydroxycholorquine, immunosuppression, and/or glucocorticoids) remain the “bread-and-butter” approach for managing lupus disease and continue to be actively researched.
Antibody based therapies typically target key immune pathways involved in disease progression more precisely than broad immunosuppressants. Existing antibody therapies like anifrolumab and belimumab have already shifted the treatment paradigm by targeting B-cell survival and type I interferon signaling, respectively. At EULAR 2025, these widely used drugs will be discussed in the context of new supporting data in the SLE treatment landscape. For example, the presentations include a data readout from the LASER study that used data from the TULIP trials and compared it to a real-world standard of care (RW SoC) cohort to evaluate the long-term effectiveness of anifrolumab in preventing organ damage. The study found that anifrolumab-treated patients resulted in 0.416 fewer points of organ damage (p < 0.001) and were 59.9% less likely to have organ damage than RW SoC patients. On belimumab, real world evidence from a Spanish multicenter registry, also to be presented at EULAR 2025, reveals that patients who started on treatment within two years of diagnosis experienced benefits such as lower disease symptoms and less organ damage over patients who were prescribed belimumab later further. This data aligns with treatment recommendations from ACR and EULAR to initiate lupus treatment with biologics early and builds on belimumab’s 10 year+ real-world and clinical data demonstrating great potential in SLE disease control.
In LN management, a severe form of SLE, one of the most notable updates at EULAR 2025 may come from the positioning of obinutuzumab, a humanized type II anti-CD20 monoclonal antibody within the EULAR recommendations that expected to be updated at the conference.
Obinutuzumab targets CD20 on B cells, leading to potent depletion through enhanced antibody-dependent cellular cytotoxicity (ADCC) and direct cell death induction- a more effective MOA than that of existing therapies due to its superior ADCC activity. Data from the Phase 3 REGENCY trial (released in 2024 and first presented at WCN 2025), builds on Phase 2 data from the NOBILITY trial and showed that obinutuzumab significantly improves complete renal response (CRR) at week 76 vs. placebo and showed no unexpected safety signals.
Due to its success in the NOBILITY (Phase 2) and REGENCY (Phase 3) trials, obinutuzumab may be positioned as an alternative to belimumab and voclosporin within the treatment paradigm of Class III/IV +/- V LN patients as outlined by the EULAR recommendation. The potential inclusion of obinutuzumab in the EULAR guidelines will align with the British Society of Rheumatology’s recommendation of obinutuzumab as one of the options in triple therapy for LN.
Apart from obinutuzumab, emerging biologics in clinical development, such as ianalumab (anti-BAFF receptor), and dapirolizumab pegol (anti-CD40L), aim to further refine B-cell depletion strategies with improved precision and durability. Furthermore, oral therapies like JAK inhibitors (e.g. upadacitinib) and TYK 2 inhibitors (e.g. deucravacitinib) are being investigated to improve adherence and convenience in chronic autoimmune conditions like SLE and LN.
Challenges and future directions:
Transient mRNA CAR-T platforms that are currently in pre-clinical research can be a promising alternative that provide efficacy and safety through tunable immune activation that is not permanent. Furthermore, the majority of upcoming and existing CAR-T therapies target CD-19, however, not all SLE patients exhibit B-cell dominant disease states. Novel biomarkers (e.g., CD22, BCMA, etc.) are increasingly under exploration to personalize therapy based on patient-specific immune phenotypes such as in GC012F.
Despite breakthroughs in antibody-based SLE therapies, continued research is important to increase the future treatment options in the space. For instance, while obinutuzumab has shown promise in LN, it was not evaluated in patients with pure Class V disease leaving a continued unmet need in this subgroup. Furthermore, there is a distinct lack of options for pregnant lupus patients. Dapirolizumab pegol may be positioned as a safe and effective treatment for pregnant people as the molecule does not easily cross the placenta due to its larger size. Finally, the development of effective oral treatment options (e.g. JAK or TYK2 inhibitors), especially for SLE, is important to provide convenient options for patients with a fear of needles.
Conclusion:
Looking forward to EULAR 2025, the congress will include some of the most innovative developments in autoimmune disease therapy, particularly for SLE and LN, where transformative approaches like next-generation CAR-T and antibody-based therapies are redefining treatment goals. These innovations signal a paradigm shift from chronic immunosuppression to durable immune reset, which paves the way for curative and personalized therapies.
