Novartis & BMS CAR-T Cell Trials on Hold Save

Reuters and the Wall Street Journal report that both Novartis and Bristol Myers Squibb (BMS) have paused their autoimmune disease CAR-T cell trials due to safety concerns, including deaths.

Novartis has halted their cellular therapy trials with rap-cel (multiple autoimmune indications) because of 3 deaths related to “serious immune effector cell-associated hemophagocytic syndrome (IEC-HS).”  "Rap-cel" is Novartis' experimental rapcabtagene autoleucel - a CD19 CAR-T cell therapy given in conjunction with lymphodepletion.    

Novartis paused eight studies including the Phase 2 AUTOGRAPH clinical trials using rap-cel in either systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies; and the Phase 1/2 trials looking at rap-cel in rheumatoid arthritis, ANCA associated vasculitis, generalized myasthenia gravis and multiple sclerosis.   Novartis plans to conduct “a comprehensive review of the observed safety events” and sharing their findings with FDA and other regulators.  Studies of rap-cel in cancer (lymphoma and leukemia) patients are continuing.

Bristol Myers acting “out of an abundance of caution,” voluntarily paused its development program for zolacabtagene autoleucel, also known as "zola-cel" (BMS-986353). citing “transient” side effects without reporting any deaths.

Bristol Myers ⁠said its ​pause was put in place after patients experienced “transient and reversible inflammatory events.”  The company added that the drug's overall safety profile remains in line with other CAR T therapies.

Both companies are developing CD19 CAR-T cell therapies but the reasons for halting drug development may not be the same. Both companies are using a rapid manufacturing platform. Some have suggested that rapid manufacturing may underlie these reported toxicities.