Novartis, Bristol Myers halt CAR-T autoimmune trials over safety concerns

Novartis ↗ 1.98% and Bristol Myers Squibb ↘ 0.10% have temporarily halted multiple clinical trials testing CAR-T cell therapies in autoimmune diseases after observing serious inflammatory side effects, the companies confirmed Monday.

Novartis initiated holds on trials of its autologous CD19 CAR-T therapy, rapcabtagene autoleucel (rap-cel), on Aug. 24 after identifying three cases of immune effector cell-associated hemophagocytic syndrome, or IEC-HS, a rare and potentially life-threatening hyperinflammatory reaction. The paused studies span eight autoimmune indications, including lupus, systemic sclerosis, myasthenia gravis, multiple sclerosis, and others.fiercebiotech+1

"The temporary halt will allow for a more comprehensive review of the evolving clinical and safety data across the program," a Novartis spokesperson said. The company added that its ongoing oncology trials of rap-cel are unaffected.biopharmadive+1

BMS Also Pauses Zola-cel Program

Separately, Bristol Myers Squibb voluntarily paused enrollment in autoimmune trials of its own CD19 CAR-T therapy, zolacabtagene autoleucel (zola-cel), citing "transient and reversible inflammatory events" detected during routine safety surveillance. A BMS spokesperson said the pause was made "out of an abundance of caution" and that the company aims to resume testing "as quickly as possible".fiercebiotech+1

Results published earlier this year had detailed one prior case of IEC-HS in a Phase 1 study of zola-cel. BMS had been set to begin a new trial of zola-cel in systemic sclerosis this month.biopharmadive

Rapid Manufacturing Under Scrutiny

Both rap-cel and zola-cel were developed using rapid manufacturing platforms — Novartis' T-Charge and BMS' NEX T, respectively. William Blair analysts suggested in a Monday note that "rapid manufacturing could be driving increased cell expansion and the reported toxicities".fiercebiotech

IEC-HS is a hyperinflammatory syndrome involving uncontrolled activation of T cells, natural killer cells, and macrophages, leading to a cytokine storm and potential multi-organ dysfunction. Reported mortality in IEC-HS cases across CAR-T and T-cell engager therapies has been high, at roughly 61%, according to a published analysis of U.S. adverse event data.pubmed.ncbi.nlm.nih+1

The setbacks come as the broader CAR-T autoimmune field continues to advance. Cabaletta Bio is preparing to submit its candidate rese-cel for approval in myositis next year, while Miltenyi Biomedicine's zorpo-cel has shown favorable safety and efficacy in autoimmune diseases without higher-grade toxicities in early studies.nature+1

In a separate but related development, BMS last week ended a $380 million manufacturing partnership with Cellares for the commercial-scale production of its CAR-T therapy Breyanzi, after Cellares' automated system failed to meet manufacturing requirements, according to Reuters.bioprocessintl+1