The company suspended the trials at the end of August. The exact time of the patients’ deaths has not yet been disclosed.
The studies evaluated the experimental CAR-T therapy rapcabtagene autoleucel, abbreviated as “rap-cel.” It was attempted to be applied to treat lupus, multiple sclerosis, and other severe autoimmune and neurological diseases.
A dangerous immune reaction recorded
The Swiss pharmaceutical company confirmed that three patients died due to complications related to severe immune effector cell-induced hemophagocytic syndrome, abbreviated IEC-HS.
This is a rare but life-threatening inflammatory reaction that can occur after immunotherapy. It is believed to be caused by the very rapid proliferation and activation of laboratory-modified T lymphocytes in the patient’s body. The resulting extremely strong immune reaction can damage organs.
A company representative stated that the trials were suspended to thoroughly evaluate accumulating clinical and safety data. Each case is being reviewed together with independent trial safety monitoring committees, and the available information is being passed on to drug regulatory authorities.
Patients already treated in the trials will continue to be monitored according to the planned protocols.
Cells are modified in the laboratory
During CAR-T therapy, immune system T lymphocytes are taken from the patient’s blood. In the laboratory, they are genetically modified to recognize a specific target and destroy disease-causing cells. Later, the modified cells are infused back into the patient’s body.
This treatment principle is already applied in some forms of blood cancer. However, scientists are investigating whether CAR-T therapy could also help people with severe autoimmune diseases that do not respond to conventional treatment.
“Rap-cel” therapy targets the CD19 protein found on the surface of B lymphocytes. These immune cells can play an important role in the development of autoimmune diseases, where the body’s immune system mistakenly attacks its own tissues.
Read more But the club that was just in the EuroLeague elite has been thrown out of the EuroCup
By removing altered or malfunctioning B cells, the aim is to essentially restart part of the patient’s immune system. Early studies showed that this method could help achieve long-term remission of hard-to-treat diseases, but the treatment is also associated with serious risks.
Tested in treating eight disease groups
Four phase two trials were stopped, in which the therapy was evaluated for treating systemic lupus erythematosus and lupus-induced kidney inflammation, systemic sclerosis, ANCA-associated vasculitis, and idiopathic inflammatory myopathies.
Four phase one and two trials were also temporarily halted. They were aimed at:
- rheumatoid arthritis and Sjögren’s syndrome,
- generalized myasthenia,
- relapsing multiple sclerosis,
- inactive progressive multiple sclerosis.
The company emphasized that “rap-cel” trials involving cancer patients are continuing. Thus, the decision is not related to all CAR-T therapies or their already approved use in oncology – only specific experimental drug trials for autoimmune and neurological diseases have been suspended.
Another company also suspended trials
Similar precautions were taken by the US pharmaceutical company Bristol Myers Squibb. It temporarily halted the enrollment of new patients in CAR-T therapy “zola-cel” trials for autoimmune diseases.
The company indicated that during routine safety monitoring, temporary and reversible inflammatory reactions were recorded. No fatal cases have been reported in these trials.
Bristol Myers Squibb hopes to evaluate the accumulated data and resume trials as soon as possible. According to the company, results obtained so far still allow hope that this therapy could help patients with systemic lupus erythematosus and other autoimmune diseases.
