Anvisa, Brazil's federal health regulator, suspended the country's clinical trials of an experimental Novartis cell therapy for autoimmune diseases on Monday (14). The order, published in the Federal Official Gazette, came 13 days after the Swiss drugmaker temporarily halted the global program for the product, rapcabtagene autoleucel (rap-cel or YTB323), following the deaths of three patients.
The decision stops human testing and the recruitment of new volunteers in Brazil. According to G1, three phase 2 protocols were testing rap-cel in patients with granulomatosis with polyangiitis, microscopic polyangiitis, systemic lupus erythematosus, lupus nephritis and diffuse cutaneous systemic sclerosis. Phase 2 mainly evaluates safety in a larger number of people. The number of volunteers already treated in Brazil has not been disclosed.
What is confirmed and what is still preliminary
It is confirmed that three deaths occurred in the global program and that Novartis attributed the severe reactions to a condition known as immune effector cell-associated hemophagocytic syndrome (IEC-HS). According to the company, cited by Folha de S.Paulo, this is a known side effect of CAR-T therapies that can cause potentially fatal complications. G1 reports that the trigger for the suspension came from outside Brazil. The analysis of what led to the deaths is still preliminary: the company says it is reviewing the cases with independent safety committees to understand why the immune response was not controlled and how warning signs can be detected earlier.
What rap-cel is
Rap-cel is a CAR-T therapy: defense cells are collected from the patient, modified in a laboratory to recognize and attack a specific target, and returned to the bloodstream. Novartis had presented the product as a therapy with the potential to "reboot the immune system". The technique is already used against some types of cancer, and the rap-cel studies in leukemia and lymphoma were not affected by the pause. According to the company, safety observed in those patients remains within the expected range for the class of drugs.
The global suspension was announced on September 1, and Endpoints News first reported the deaths on the night of August 31, according to Folha de S.Paulo, which ran a Bloomberg report. Also in response to the cases, Bristol Myers Squibb said it had suspended similar trials of its CAR-T for autoimmune diseases, zola-cel, "out of an abundance of caution". G1 sought comment from Novartis on the Anvisa decision and had received no reply by publication.
In practical terms, clinical follow-up of volunteers already treated in the Brazilian protocols must continue, since the suspension applies to new procedures and recruitment. Anyone taking part in the study, or following someone who does, can contact the research center responsible for answers. Established uses of the technique against some types of cancer are not affected by this decision.