Allogene Halts ALLO-647 Development After Patient Death in Lymphoma Trial

Allogene Therapeutics has announced the discontinuation of its immunosuppressive antibody ALLO-647 following a patient death in its pivotal Phase II ALPHA3 trial. The trial was evaluating cemacabtagene ansegedleucel (cema-cel), an investigational CAR T therapy for the treatment of large B-cell lymphoma.

Patient Mortality Linked to ALLO-647

The patient death, which occurred 54 days after infusion, was attributed to liver failure resulting from disseminated adenovirus infection. Allogene stated that the mortality was not directly linked to cema-cel but rather to ALLO-647, a monoclonal antibody targeting the CD52 protein used as a lymphodepletion therapy to prepare patients for cema-cel treatment.

According to the company, severe infections have been rare across Allogene's trials. However, when present, they have been attributed to immunosuppression due in part to ALLO-647. This event has led Allogene to discontinue the study arm using ALLO-647 as part of the immunosuppressive regimen and remove the antibody from its pipeline entirely.

Impact on ALPHA3 Trial and Future Plans

In response to this development, Allogene will proceed with the ALPHA3 trial using only fludarabine and cyclophosphamide (FC) as lymphodepletion treatments for patients receiving cema-cel. The company expects to conduct a futility analysis for ALPHA3 in the first half of 2026.

Analysts at William Blair supported Allogene's decision to discontinue the FCA (fludarabine, cyclophosphamide, and ALLO-647) regimen in the ALPHA3 study. However, they cautioned that the standard lymphodepletion regimen with FC might not lead to as robust cema-cel expansion and persistence compared to when ALLO-647 is added to the regimen.

Despite this setback, the analysts noted that patients enrolled in ALPHA3 have lower burdens of disease, suggesting that an enhanced lymphodepletion regimen may not be necessary. They also speculated that moving forward with just the FC regimen could potentially lead to higher commercial uptake for cema-cel, if approved, due to lower safety risks.

Market Reaction and Future Outlook

The news of the patient death and subsequent pipeline changes had an immediate impact on Allogene's stock, which dropped 12% in trading on Friday. As the company navigates this challenging situation, the pharmaceutical industry will be closely watching the progress of the ALPHA3 trial and the potential implications for CAR T therapies in the treatment of large B-cell lymphoma.