After a CD19-targeting CAR-T therapy reset her B cells, a woman with three different autoimmune diseases is now in remission.\n A CAR-T cell therapy has successfully treated not one, not two, but three different autoimmune diseases at once in a patient, providing further proof of the modality’s promise in the disease area as a likely first approval fast approaches.The patient, a 47-year-old woman, was first diagnosed with autoimmune hemolytic anemia (AIHA) in 2014, and the illness persisted even after nine different therapies. She later developed antiphospholipid syndrome (APLAS) and immune thrombocytopenia (ITP), unrelated conditions that are all caused by B cells producing rogue antibodies that attack the body.“She probably was unlucky,” Fabian Müller, M.D., Ph.D., head of the CAR-T unit at University Hospital Erlangen in Germany, where the patient was eventually treated, told Fierce. “There is flavors of that that co-occur frequently, but that somebody has these three diseases in parallel, it\'s quite uncommon.”After receiving Miltenyi Biomedicine’s zorpocabtagene-autoleucel (zorpo-cel), a CD19-targeting investigational cell therapy where a patient’s T cells are extracted and engineered to attack B cells before being reinfused, all three of the patient’s conditions are now under control. What’s more, the treatment led to no cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, which are common severe side effects of other CAR-T therapies when used to treat blood cancers.Müller and colleagues detailed the case in the journal Med on April 9.Before receiving zorpo-cel, the patient required regular hospitalization. Her AIHA caused antibodies to destroy her red blood cells, leading to anemia and jaundice, while APLAS and ITP similarly led to her immune system attacking fat cells and platelets, respectively. Now, 11 months later, the patient is in remission and leading a normal daily life, with no need for blood transfusions to replace the red blood cells her antibodies previously destroyed. Those regular transfusions caused her iron levels to spike, and she now needs weekly blood-letting to steadily drain the metal out of her system.By targeting B cells, zorpo-cel essentially “resets” the patient’s immune system, with healthy B cells replacing their disease-causing predecessors. “I expected all three diseases to go away,” Müller said. “The question is whether one of them comes back.”The idea of resetting the immune system has caught fire recently, with numerous players attempting to refresh immune cells using CAR-T cells or other approaches like T-cell engagers.With zorpo-cel, Miltenyi is likely the furthest ahead in lupus, Müller explained. The biotech is currently recruiting for two phase 1/2 trials in lupus indications. But the most likely biotech to achieve the first-ever autoimmune CAR-T approval is Kyverna Therapeutics, for the rare disease stiff-person syndrome. Kyverna plans to submit its candidate, miv-cel, for FDA approval in the first half of this year.T-cell engagers have emerged as a potential rival approach to CAR-T for immune system reset, with established pharma companies like Gilead Sciences and UCB buying into the space and startups like Candid Therapeutics and Oblenio Bio attempting to make a name for themselves. “All of these B cell-directed treatments are efficacious,” Müller said. “If you deplete B cells deep enough, you see a response.” But because they can penetrate deeply into tissues and reach more B cells, CAR-T therapy is the most promising approach in development, he said.As an example, he highlighted another case in which his team used a CD19-targeting CAR-T from Miltenyi to treat a patient with ulcerative colitis, the first time a CAR-T was successfully used for the disease. That patient’s disease hadn’t responded to any prior treatments, including Amgen’s first-in-class T-cell engager Blincyto.“There is nothing that depletes [B cells] as deeply as CARs, period,” Müller said.
