More Than Half of Patients With Lupus Achieve Remission in Early Trial of Off-the-Shelf CAR T Therapy

Early clinical results show that more than half of patients with lupus achieved symptom remission after a single dose of an off-the-shelf CAR T-cell therapy.

Adicet Bio announced the results from a phase 1 trial of its allogeneic, off-the-shelf cell therapy, prula-cel, according to U.S. biotech publication Fierce Biotech on the 25th (local time).

At the 1-year assessment, 12 of 22 evaluable patients had achieved remission of lupus symptoms. Among 16 patients with lupus nephritis, 8 had renal symptom remission.

Lloyd Klickstein, Adicet Bio’s interim chief medical officer, said, “Patients who had failed multiple prior treatments achieved remission after a single dose of prula-cel. Remission occurred without immunosuppressants and was accompanied by biological evidence of immune resetting.”

Notably, no fatal adverse events occurred. Novartis’ CD19-targeted CAR T candidate, lap-cel, recently faced disruption to its program after three deaths from immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS).

Bristol Myers Squibb (BMS) also paused a trial of its CD19-targeted CAR T therapy, zola-cel, citing “transient and reversible inflammatory reactions.” Unlike lap-cel and zola-cel, which are patient-derived (autologous) therapies, prula-cel is an off-the-shelf product.

Adicet Bio said there were no cases of IEC-HS or immune effector cell-associated neurotoxicity syndrome (ICANS) with prula-cel, and that most cases of cytokine release syndrome (CRS) were grade 1. Both are common complications of CAR T therapy.

Unlike other CAR T therapies, prula-cel uses a rare subtype of T cell called a gamma delta T cell. Chen Schor, Adicet Bio’s CEO, told Fierce Biotech, “These cells do not circulate in the bloodstream; they are naturally present in the body’s tissues. That could be an advantage because autoimmune diseases ultimately arise in organs.”

Prula-cel targets CD20 on B cells, which produce antibodies. The company said it had observed early signs of immune resetting, with newly generated B cells returning after treatment as “naive B cells” that do not cause disease.

“The B cells that return after resetting are naive B cells unrelated to the disease,” Schor said. “That is the definition of resetting.”

The company added that all patients in the trial stopped taking standard immunosuppressants, even if they did not achieve complete remission, and all but one substantially reduced their steroid dose.

Adicet Bio plans to develop prula-cel as a “one-and-done” treatment option for lupus. The U.S. Food and Drug Administration has agreed to a single-arm confirmatory trial in lupus nephritis, which is expected to begin next year. The company expects to later expand the trial to patients with lupus who do not have kidney disease.

With several CAR T therapies already approved for blood cancers, autoimmune diseases have emerged as the next frontier. Kyverna Therapeutics, which is developing a treatment for stiff person syndrome, is pursuing a rolling FDA submission that is expected to be completed this year.

Schor said, “This could be a new era for autoimmune diseases,” similar to the emergence of tumor necrosis factor (TNF)-targeted drugs more than 20 years ago.