Zolacaptagene Autoleucel

iStock, cagkansayin Not a month after reports of three deaths in autoimmune trials for Novartis’ CAR T cell therapy ignited a debate about the use of these treatments in nonfatal diseases, Kyverna Therapeutics reported data bolstering its case to bring to market the first CAR T for an autoimmune disease. Significant safety setbacks and subsequent trial suspensions of several autoimmune CAR T therapy trials at Novartis and Bristol Myers Squibb have given analysts pause—and reason to question the suitability and business prospects of using these treatments in typically nonfatal conditions. But continued success by Kyverna Therapeutics has reignited enthusiasm for the idea. Novartis confirmed to BioSpace last month that it has paused several studies of its CAR T candidate rapcabtagene autoleucel, or rap-cel, in autoimmune diseases after the deaths of three patients who received the therapy. BMS followed suit, voluntarily freezing autoimmune trials of its own CAR T asset zolacabtagene autoleucel (zola-cel) after observing “transient and reversible inflammatory events,” the pharma told William Blair analysts, per an Aug. 31 note. Analysts were quick to react to the news, noting that the use of CAR T therapies in autoimmune disease may not be a sound bet. “We believe that the emergence of serious immune-related toxicities—including three patient deaths for rapca-cel (NVS)—adds considerable uncertainty to the auto-CAR-T use case in [autoimmune disease],” Leerink Partners wrote in a note to investors on Sept. 1. Some drug developers had already arrived at this conclusion. CAR T therapy in autoimmune disease “was never really supposed to happen because CAR Ts were always perceived to be more on the oncology side,” said Sanjeev Luther, CEO of Ernexa Therapeutics, which is developing cell therapies for ovarian and other cancers. “What you look for in oncology in terms of tox versus efficacy, that equation is so different than what you would see in autoimmune diseases.” In most cancers, Luther told BioSpace , “the outcome is not good . . . whereas autoimmune diseases, they’re chronic. People are not necessarily dying. Quality of life is terrible, but they live.” Kate Rochlin, president and COO of IN8bio, pointed out that this risk factor is not new. “The risk of cytokine secretion and overactivation of the immune system has always been there” with CAR T therapies, she told BioSpace . But she agreed that, in oncology, “the risk-benefit ratio made sense,” as some patients are “definitely going to die from a tumor.” As CAR T began to move into the autoimmune space, “we had to assess how that risk-benefit ratio shapes out and how it changes,” she added. Enter Kyverna Therapeutics, which continues to move closer to the first CAR T approval in this space with a therapy called mivocabtagene autoleucel (miv-cel) that has improved mobility and reduced disability in patients with stiff person syndrome (SPS), a rare, progressive neurologic autoimmune disease. Importantly, the investigational CAR T has posted a solid safety profile. While autoimmune conditions are typically not fatal, Kyverna CEO Warner Biddle said the disease burden is underappreciated, particularly in SPS. “Over 80% of patients will become debilitated and either require a walker or a wheelchair at some point in their diagnosis,” he told BioSpace . “Less than 20% of them actually will remain employed four years after their diagnosis.” CAR-T Novartis pauses CAR T studies due to 3 deaths; BMS follows suit after safety events Novartis suspended multiple studies of a CAR T candidate after three patients who received the therapy suffered fatal cases of immune effector cell-associated hemophagocytic syndrome. BMS, meanwhile, paused some CAR T trials after separately observing “transient and reversible inflammatory events” with its therapy. September 1, 2026 · 3 min read · Tristan Manalac Read more The CAR T buzz in autoimmune CAR T exploded onto the autoimmune disease scene in late 2023 when Georg Schett and colleagues presented data at the American College of Rheumatology’s Convergence in November 2023 showing that a B cell–targeting CAR T therapy led to disease remission in eight patients with systemic lupus erythematosus (SLE) after up to two years of follow-up. The study was published in The New England Journal of Medicine in Feb. 2024. Three patients with idiopathic inflammatory myositis and four patients with systemic sclerosis also saw improvement on disease-specific scales. “To us, it seemed like every single one of our CAR T competitors and colleagues became an autoimmune company overnight,” IN8bio Founder and CEO Will Ho told BioSpace . “I think oncology and autoimmune are almost like two sides of the same coin,” he added. “If I have an overactive immune system, I’m going to get autoimmune disease. But if I repress the immune system enough, I’m going to get immune escape of transformed cells, and I get a cancer.” The autoimmune space is “a massive business proposition” for CAR T developers, Luther said. Rather than treating 100,000 patients with cancer, companies can think about treating millions of patients with autoimmune disease, he added. More than two years on from that NEJM publication, there are still no FDA-approved CAR T therapies for autoimmune disease—but Kyverna Therapeutics is knocking on the door. The California-based biotech is on track to complete a rolling biologics license application (BLA) for miv-cel in SPS by the end of this year. Last month, Kyverna reported one-year durability data from its registrational, Phase 2 KYSA-8 trial showing that miv-cel improved mobility and leg function in 26 patients with SPS. Miv-cel was well-tolerated, with no cases of high-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), according to a Sept. 24 press release . There were also no cases of immune effector cell-associated hemophagocytic lymphohistiocytosis–like syndrome (IEC-HS)—the life-threatening hyperinflammatory syndrome that led to the three deaths following treatment with Novartis’ rap-cel. Drug Development Kyverna steps closer to FDA-first CAR T for an autoimmune condition with durability data Kyverna Therapeutics’ miv-cel showed improved mobility and a favorable safety pro one year in patients with stiff person syndrome, further derisking an upcoming FDA application, William Blair said on Thursday. The biotech plans to priority review this year. September 24, 2026 · 3 min read · Heather McKenzie Read more So why is Kyverna seemingly sailing toward a BLA filing while Novartis and BMS are pausing autoimmune trials of their respective candidates? Ho said he believes the safety concerns with both rap-cel and zola-cel are specifically related to some of Novartis’ and BMS’ rapid expansion protocols. In both cases, CMC modifications have been made to shorten the time from T cell collection to infusion of the engineered cells back into the patient, Ho continued, leading to “much more rapid expansion of the cells.” Without knowing the characteristics of the cells and how they are stimulated, he said it would make sense that “some of those processes might stimulate a T cell to secrete more cytokines than they otherwise would have.” Meanwhile, Biddle attributed miv-cel’s positive safety pro a well-established manufacturing process and the “unique” design of the construct, noting that the therapy is the only CD19 CAR T in the autoimmune space that has a fully human CD28 co-stimulatory domain that was specifically designed for safety. In light of the recent safety signals at Novartis and BMS, Luther insisted that it’s important to not lump all cell therapies together. “I think the human tendency always has been [that] all cell therapies are the same, but they are not,” he said. “The safety signals emerging in one modality should be taken seriously, but they should not be extrapolated across an entire field that encompasses a wide range of cellular technologies.”