Cell and Gene Therapy: A Transformative Shift
Chimeric antigen receptor (CAR) T-cell therapy is an exciting, potentially curative development for lupus. This approach modifies a patient's own T cells to target disease-causing B cells, showing promising early results for severe systemic lupus erythematosus (SLE).
Promising CAR-T Programs in 2025
Several biotech companies are advancing their CAR-T programs for refractory SLE and lupus nephritis (LN):
- Fate Therapeutics (FT819): Received RMAT designation from the FDA in April 2025 for its 'off-the-shelf' CAR-T therapy for moderate to severe SLE, including LN.
- Allogene Therapeutics (ALLO-329): Gained Fast Track designation from the FDA in April 2025 for refractory moderate-to-severe SLE, with a Phase 1 study including LN patients planned for mid-year.
- Adicet Bio (ADI-100): Received Fast Track designation for refractory SLE in February 2025.
- Sana Biotechnology (SC291): Granted Fast Track status for relapsed/refractory SLE in December 2024.
- Cabaletta Bio (CABA-201): Showed positive Phase 1/2 data in late 2024 in patients with SLE and LN.
Challenges and Considerations for CAR-T Therapy
Currently, CAR-T therapy for lupus is experimental and studied in small groups with severe, resistant disease. Challenges include long-term safety, high cost, and identifying suitable patients. Research continues to explore ways to improve accessibility.
Advancements in Targeted Biologics
Targeted biologics remain crucial for lupus, with several agents progressing towards wider availability in 2025.
Obinutuzumab for Lupus Nephritis
In March 2025, the FDA accepted a sBLA for obinutuzumab (Gazyva®) for lupus nephritis. Based on Phase 3 data, this anti-CD20 antibody improved renal response when combined with standard therapy, offering a targeted option for kidney complications. Obinutuzumab is designed for more effective B cell depletion.
Subcutaneous Anifrolumab for SLE
Anifrolumab (Saphnelo®), a type I interferon receptor antagonist, may become more convenient. In September 2025, a subcutaneous (SC) formulation was submitted for approval following positive Phase 3 results. This would allow for at-home administration.
The Evolving Pipeline for Lupus and LN
The lupus pipeline is active, with therapies targeting various aspects of the disease.
Other Biologics and Small Molecules in the Pipeline
- Litifilimab (Biogen): An antibody targeting BDCA2, in Phase 3 trials for cutaneous and systemic lupus.
- Ianalumab (Novartis): A BAFF-R inhibitor in Phase 3 for SLE and LN.
- Upadacitinib (AbbVie): A JAK1 inhibitor in Phase 3 trials for SLE.
- KPG-818 (Kangpu Biopharma): An oral small molecule for skin manifestations, in Phase 2b.
Sustained Outcomes with Existing Agents
Recent 2025 data supports the benefits of existing therapies. Long-term studies confirmed voclosporin's effectiveness and safety for LN over three years. Studies also reinforced belimumab's benefits in LN patients.
Comparison of Novel Lupus Treatments
| Feature | CAR-T Cell Therapy | Obinutuzumab (Gazyva®) | Subcutaneous Anifrolumab (Saphnelo®) | Targeted Biologics (e.g., Litifilimab) |
|---|---|---|---|---|
| Mechanism of Action | Re-engineers T cells to target and eliminate CD19+ B cells. | Anti-CD20 antibody that depletes B cells. | Monoclonal antibody that blocks the type I interferon receptor. | Target specific immune pathways (e.g., BDCA2) to block inflammatory signals. |
| Status in 2025 | Experimental, Phase 1/2 trials for severe refractory cases. | Regulatory review by FDA for lupus nephritis indication. | Regulatory review by FDA for subcutaneous formulation. | Various stages, several in Phase 3 trials. |
| Indicated For | Severe, refractory SLE and LN in clinical trials. | Potential for lupus nephritis if approved. | Moderate to severe SLE. | Specific SLE or cutaneous lupus manifestations. |
| Potential Impact | Long-term, potentially curative remission for severe cases. | Provides an additional, effective option for LN. | Offers more convenient at-home administration. | Offers more personalized, pathway-specific treatment. |
Conclusion: A Shift Towards Personalized Medicine
In 2025, lupus treatment is moving towards targeted and personalized approaches. CAR-T therapy offers potential breakthroughs for severe cases, while advances in biologics like obinutuzumab and subcutaneous anifrolumab improve immediate patient care. Future strategies will likely use biomarkers and genetic profiling to tailor therapies, aiming to improve outcomes and quality of life for those with lupus.
