As the race to harness CAR-T cells for autoimmune diseases hits a rough patch, a Bay Area biotech is gliding over the potholes with an early sign of efficacy in lupus.
Adicet Bio today reported that its off-the-shelf cell therapy prula-cel sent more than half of patients’ lupus into remission in a small phase 1 trial, without the dangerous and potentially deadly side effects that recently rocked Big Pharma.
One year after treatment, 12 of the 22 evaluated patients had achieved remission of their lupus symptoms, and eight of the 16 of those patients with lupus nephritis saw remission of their kidney symptoms.
The remissions came “after a single dose of prula-cel in patients who had failed multiple prior therapies,” Lloyd Klickstein, M.D., Ph.D., Adicet’s interim chief medical officer, said in a release. “Notably, these remissions were achieved off immunosuppression and were accompanied by biological evidence of an immune reset.”
Critically, the company also reported no cases of immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a serious hyperinflammatory condition that recently caused three deaths in Novartis’ autoimmune program for the CD19-targeted CAR-T candidate rap-cel.
BMS, too, recently paused trials of its CD19-targeted CAR-T zola-cel due to “transient and reversible inflammatory events.” Both rap-cel and zola-cel are derived from patients, rather than being off-the-shelf like prula-cel.
Adicet also reported no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), and almost all instances of cytokine release syndrome (CRS) were grade 1. Both ICANS and CRS are common complications of CAR-T therapy.
Unlike other CAR-T cell therapies, prula-cel consists of an uncommon subtype of T cells called gamma delta T cells. These cells, Adicet CEO Chen Schor explained to Fierce, naturally reside in the body’s tissues rather than circulating in the bloodstream.
“That makes them potentially very favorable for autoimmune diseases because, at the end of the day, the disease happens in the organs,” Schor said.
Prula-cel also goes after CD19 expressed on B cells, the antibody-producing immune cells that go rogue in autoimmune diseases like lupus. Adicet is seeing early signs that the therapy successfully resets the patient’s immune system, with newly created B cells not showing signs of causing disease.
“The B cells that come back after this reset, they come as naive B cells,” Schor told Fierce. “These are B cells that are not associated with the disease, and that is really the definition of a reset.”
All patients evaluated in the study, even those who didn’t achieve full remission, have stopped taking their standard immunosuppressants, Schor added, and all but one have significantly reduced their dosage of steroids.
Rather than relying on this “cocktail” of therapies, Adicet plans to further develop prula-cel as a one-and-done treatment option for lupus. The FDA has already agreed to a single-arm pivotal trial for lupus nephritis that should start next year, Schor said, and will likely then expand to include lupus patients who don’t have any kidney disease.
With multiple CAR-T therapies already approved for blood cancers, autoimmune diseases have become a major next frontier for the approach. A first approval is likely coming soon, with Kyverna Therapeutics’ candidate for stiff-person syndrome—the rare disease that afflicts Céline Dion—currently undergoing a rolling submission to the FDA that should wrap up by the end of the year.
Similar to the debut of drugs targeting tumor necrosis factor more than 20 years ago, Schor said, “this might be a new era in autoimmune diseases.”