Allogene, in its pivotal Phase II trial, is evaluating cemacabtagene ansegedleucel, a CAR T therapy designed for treating large B-cell lymphoma. Within this trial, the company had incorporated ALLO-647 as a preparative lymphodepletion therapy. Unfortunately, a patient enrolled in the ALPHA3 trial of cemacabtagene ansegedleucel passed away.
The patient’s death was not directly linked to the CAR T therapy itself but was associated with ALLO-647, a monoclonal antibody aimed at the CD52 protein. This antibody was being utilized by Allogene to induce lymphodepletion in patients before administering cemacabtagene ansegedleucel. The cause of death was liver failure triggered by disseminated adenovirus infection, occurring due to immune suppression related to ALLO-647, as reported by Allogene.
Following this incident, Allogene experienced a significant drop in stock value, declining by 12% during Friday’s trading session. In response to the mortality, the company has opted to discontinue the use of ALLO-647 in the study arm and remove the antibody from its development pipeline. Instead, Allogene will proceed with fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen for patients receiving cemacabtagene ansegedleucel, anticipating a futility analysis for ALPHA3 by the first half of 2026.
Analysts, acknowledging the unfortunate event, supported Allogene’s decision to cease the FCA regimen and expressed concerns that the standard FC regimen might not achieve the same robust expansion and persistence of cemacabtagene ansegedleucel as seen with the inclusion of ALLO-647. Nevertheless, they highlighted that patients in the ALPHA3 trial have lower disease burdens, suggesting that an intensified lymphodepletion regimen may not be imperative. Furthermore, proceeding with only the FC regimen could potentially enhance the commercial viability of cemacabtagene ansegedleucel upon approval due to reduced safety concerns.
Key Takeaways:
– Allogene discontinued the use of ALLO-647 in its lymphoma trial following a patient’s death, attributed to liver failure from immune suppression.
– The company will now rely solely on fludarabine and cyclophosphamide for lymphodepletion in patients receiving cemacabtagene ansegedleucel.
– Analysts supported Allogene’s decision but expressed concerns about the impact on the therapy’s expansion and persistence without ALLO-647.
– The patient cohort’s lower disease burdens in the trial may render intensified lymphodepletion unnecessary, potentially streamlining the therapy’s commercial adoption.
Tags: biotech, cell therapy
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