A chromosome problem has been detected in one patient treated with an experimental off-the-shelf cell therapy from Allogene Therapeutics, prompting the FDA to halt all of the company’s clinical trials while the cause and significance of the issue is investigated.
Allogene said Thursday that the clinical holds came after it notified the FDA of what the company described as a “chromosomal abnormality.” A total of seven Allogene programs have reached human testing, all of them in early clinical development. Speaking on a conference call, Allogene CEO David Chang said it’s too soon to know what needs to happen for the studies to resume, but he added that it was “a bit of a surprise” that the FDA placed holds on all of the clinical trials.
Shares of South San Francisco-based Allogene sank more than 32% in after-hours trading.
The problem was detected in a patient who was receiving treatment for follicular lymphoma that had not responded to earlier treatment from chemotherapy or radiation therapy. According to the company, the patient could not receive autologous CAR T cell therapy, made from that patient’s own cells, because the expansion step of the manufacturing process did not yield enough cells.
Allogene’s cell therapies are well-suited for such cases. Instead of making the therapy from a patient’s own cells, these allogeneic, or off-the-shelf, treatments are made from the immune cells of heathy donors; these engineered cells stand ready for use when needed. Allogene said that after infusion with the experimental therapy ALLO-501A, the patient experienced an immune response called cytokine release syndrome as well as neurotoxicity—both known side effects of CAR T therapy. Those side effects were treated with steroids.
The patient also developed lower levels of platelets and red and white blood cells in the blood, which is another known CAR T complication. A bone marrow biopsy conducted to assess the low blood counts was what detected the Allogene CAR T cells with the chromosomal abnormality. Rafael Amado, Allogene’s executive vice president of research and development and chief medical officer, said that a fraction of the cells were detected with the abnormality. Chang said the abnormality was observed on chromosome 14 but additional details are still under investigation.
“This is a single case report out of more than 100 patients that we have tried,” Chang said. “This is not something that we normally look for because most patients do recover, and CAR T cells disappear from the patient’s body.”
The patient’s response to treatment with Allogene’s cell therapy was a partial one, so an allogeneic stem cell transplant was needed. This rescue treatment has been done previously in some cases of autologous CAR T.
The study in which the chromosomal problem was found is the Phase 1 portion of a Phase 1/2 test evaluating ALLO-501A, the company’s most advanced cell therapy candidate. Allogene had been working with the FDA on the design of the pivotal Phase 2 portion of the study, which was expected to begin at the end of this year.
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