Zolacaptagene Autoleucel

iStock, cagkansayin 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. Three patients have died after receiving Novartis’ CAR T candidate rapcabtagene autoleucel, prompting the pharma to suspend several immunology and neurology studies of the investigational therapy. Bristol Myers Squibb has taken a similar move, voluntarily freezing autoimmune trials for its own CAR T asset zolacabtagene autoleucel after observing “transient and reversible inflammatory events,” the company told William Blair analysts. “Emergence of [adverse events] in NVS and BMY autoimmune trials highlight risks but could reduce competition in a crowded CAR-T space,” the analysts wrote in a note to investors on Monday afternoon. A Novartis spokesperson confirmed the pause to BioSpace in an email statement on Monday afternoon, adding that the decision stemmed from three cases of “serious immune effector cell-associated hemophagocytic syndrome (IEC-HS).” These events then led to complications that eventually proved fatal. BMS, acting “out of an abundance of caution,” has also decided to voluntarily freeze at least some studies of zolacabtagene autoleucel (zola-cel), a spokesperson confirmed to BioSpace via email. The pause will allow the pharma to review clinical data across zola-cel’s development program. The pause for Novartis’ rapcabtagene autoleucel (rap-cel) affects the Phase 2 AUTOGRAPH studies in various autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies, the company’s spokesperson said. Novartis is also suspending Phase 1/2 trials looking at rap-cel’s safety, efficacy and cellular kinetics in patients with rheumatoid arthritis, generalized myasthenia gravis and certain types of multiple sclerosis. Opinion CAR T for autoimmune disease benefits from oncology’s lessons—and will deliver its own Thanks in part to the revolution cell therapy brought to treating blood cancers, the modality is now showing promise in some autoimmune applications. This expansion is poised to yield even wider benefits. August 28, 2026 · 6 min read · Deborah Phippard Read more Studies of rap-cel in cancer are unaffected by the pause, Novartis said. The pharma is currently analyzing the safety data to identify all factors that could have led to the complications. The pharma is also engaging with independent data committees to come up with better safety measures, such as tighter monitoring, earlier identification and appropriate management, the spokesperson added. As for BMS, it remains unclear if the suspension covers all of zola-cel’s studies. The pharma has several programs for the asset, including for myasthenia gravis, multiple sclerosis, rheumatoid arthritis and other immune indications. “We are focused on completing our evaluation and resuming enrollment as quickly as possible,” the spokesperson said. The exact nature of the safety events that prompted BMS’s move to pause hasn’t been disclosed. The pharma didn’t report deaths linked to zola-cel, though William Blair pointed out that at least one case of IEC-HS has previously been reported for the CAR T candidate. “IEC-HS is a rare but serious side effect that has been reported with CD19 and BCMA CAR-T therapies across blood cancer indications,” William Blair explained. While the exact causes of the IEC-HS cases remain unknown, the analysts noted that rapid manufacturing—a feature of both rap-cel and zola-cel—could play a role. “Rapid manufacturing could be driving increased cell expansion and the reported toxicities,” they posited, but added that “other factors could be playing a role . . . such as specific indications or patients harboring a predisposition to a hyperinflammatory state.” The firm cautioned that “it is difficult to extrapolate the risk of this side effect to all ongoing CAR-T programs in development for autoimmune diseases,” but listed several companies that are developing CD19 CAR Ts for autoimmune diseases. These include Autolus, Cabaletta Bio, CRISPR Therapeutics, Kyverna Therapeutics and Allogene Therapeutics. The analysts speculate how “different safety profiles may provide advantages if Bristol Myers and Novartis are limited in the development of their CAR-T programs for autoimmune diseases.”

Three deaths have forced Novartis to pause development of its CD19 CAR-T candidate in autoimmune diseases, just as Bristol Myers Squibb has halted a similar program due to immune-related adverse events, Fierce has learned. The Swiss pharma has temporarily halted development of its autologous CD19 CAR-T therapy, rapcabtagene autoleucel (rap-cel; YTB323), for several autoimmune diseases in immunology and neuroscience, Novartis confirmed with Fierce on Monday. The decision comes after the rap-cel program recorded three deaths from complications caused by serious immune effector cell-associated hemophagocytic syndrome (IEC-HS), according to Novartis. IEC-HS is a severe systemic inflammatory side effect associated with immunotherapies like CAR-T cell therapy. The rogue immune response may be triggered when engineered T cells rapidly expand and activate inside the patient’s body. Novartis confirmed the trials included phase 2 studies of rap-cel in systemic lupus erythematosus/lupus nephritis (CYTB323J12201), systemic sclerosis (CYTB323K12201), ANCA-associated vasculitis (CYTB323I12201) and idiopathic inflammatory myopathies (CYTB323L12201), as well as phase 1/2 studies evaluating safety, cellular kinetics and efficacy in rheumatoid arthritis and Sjogren’s disease, generalized myasthenia gravis, relapsing multiple sclerosis (MS), and non-active progressive MS (CYTB323M12101B, CYTB323O12101, CYTB323N12101 and CYTB323R12101, respectively). Screening, randomization and treatment administration across the studies have been put on hold, the spokesperson said. “The temporary halt will allow for a more comprehensive review of the evolving clinical and safety data across the program, following three serious immune effector cell-associated hemophagocytic syndrome (IEC-HS) events,” Novartis told Fierce in an email. “Patient safety remains of [the] highest priority; patients who have been treated within the trials will continue to be monitored as per protocol.” The company said the ongoing program in oncology , which is currently in phase 1/2 trial for chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma, adult acute lymphoblastic leukemia and high-risk large B-cell lymphoma, “is not affected by this halt.” Rap-cel is an autologous CD19-targeted CAR-T aimed to reprogram patient’s own T cells to eliminate CD19-expressing B cells. This asset is manufactured using Novartis’ T-Charge platform, a rapid manufacturing platform that allows for fewer exhausted T cells and eliminates the need for extended culture time outside of the body, according to the website . In a Monday note to clients, William Blair analysts also flagged that BMS paused enrollment in its autoimmune trials testing an autologous CD19-targeted CAR-T, zola-cel (BMS-986353). William Blair noted that in a follow-up, the company disclosed that the enrollment was paused due to “transient and reversible inflammatory events.” “Out of an abundance of caution, we implemented a voluntary pause to review clinical data across our zola-cel program,” a BMS spokesperson told Fierce in an email. “We are focused on completing our evaluation and resuming enrollment as quickly as possible.” Also targeting CD19, zola-cel acts through the same mechanism as BMS’ Breyanzi, an FDA -approved treatment for relapsed and refractory blood cancers. Like rap-cel, zola-cel was also developed using a rapid manufacturing platform. BMS’ NEXT T platform is designed to encourage the growth of more uniform and potent T cells, which may prompt a deeper and more durable response in patients, according to its website. Since both Novartis’ and BMS’ assets were developed using rapid manufacturing platforms, analysts from William Blair suggested “that rapid manufacturing could be driving increased cell expansion and the reported toxicities.” The CD19 CAR-T development space is already quite saturated, as Cabaletta Bio, a Philadelphia-based biotech, is looking to submit its autologous candidate, resecabtagene autoleucel ( rese-cel ), for approval in the second half of next year to treat myositis, a condition characterized by inflammation of the muscles. Back in April, Miltenyi Biomedicine showed that its asset, zorpocabtagene-autoleucel (zorpo-cel), drove three autoimmune diseases into remission in one patient. Fate Therapeutics also recently reported improvements in patients with treatment-resistant systemic sclerosis who were dosed with its off-the-shelf candidate, FT819. Editor's Note: The story was updated Aug. 31 at 10:10 p.m. ET to reflect that the three serious IEC-HS cases in Novartis' program were deaths.