Rockville, Maryland-based AbelZeta Pharma has received US FDA clearance to proceed with a multi-center registrational Phase II trial of C-CAR168, an autologous bispecific CAR-T cell therapy, in patients with lupus nephritis refractory to standard treatment. The clearance was granted under AbelZeta's existing IND — originally cleared in May 2024 — and facilitated through the FDA's Regenerative Medicine Advanced Therapy (RMAT) designation, which the agency awarded to C-CAR168 in May 2025. The move positions AbelZeta to generate pivotal efficacy data in a patient population for which no approved therapy currently exists. Registrational Phase II studies remain relatively uncommon and may, if sufficiently persuasive, support regulatory submissions in areas of high unmet medical need.
Lupus nephritis, a serious renal manifestation of systemic lupus erythematosus (SLE), affects up to 50% of SLE patients and carries a meaningful risk of progressive kidney failure. While four biologics have received FDA approval for active LN or SLE — GSK's belimumab (Benlysta), Aurinia Pharmaceuticals' voclosporin (Lupkynis), AstraZeneca's anifrolumab-fnia (Saphnelo), and Genentech's obinutuzumab (Gazyva), approved most recently in October 2025 — all are studied in patients receiving background immunosuppressive therapy and none are validated for patients who have failed multiple prior induction regimens. Patients with refractory disease therefore have limited options beyond escalating immunosuppression.
C-CAR168 is engineered to simultaneously target CD20, expressed on mature B cells and plasmablasts, and BCMA, expressed on long-lived plasma cells. This dual-target design attempts to address a mechanistic limitation of existing therapies: agents such as obinutuzumab deplete CD20-expressing B cells but leave BCMA-positive plasma cells intact, allowing continued secretion of pathogenic autoantibodies. By targeting both cell populations in a single construct, C-CAR168 is designed to achieve a more complete depletion of the autoreactive B-cell lineage and, in principle, an immune reset rather than ongoing disease suppression.
Phase I data from an investigator-initiated trial (NCT06249438), presented at ACR Convergence and LUPUS 2025, included a small cohort of refractory LN patients. AbelZeta has not disclosed detailed efficacy or safety outcomes from those presentations in the current announcement, but the data were sufficient to support progression to a company-sponsored registrational Phase II design. The forthcoming trial will enroll patients across multiple centers and is intended to evaluate both safety and efficacy as the basis for a potential regulatory submission.
C-CAR168 also holds EMA PRIME designation for refractory SLE including LN, granted in July 2026, providing a parallel expedited development pathway in Europe. AbelZeta described plans to advance the program globally, and noted active evaluation of C-CAR168 in additional autoimmune indications, including progressive multiple sclerosis.