Allogene Halts ALLO-647 Development Following 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 study 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 CAR T 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. The biotech emphasized that available evidence supports the event was caused by ALLO-647-mediated prolonged T-cell suppression rather than cema-cel itself.

Strategic Shift in Clinical Development

In response to this setback, Allogene has decided to discontinue the study arm using ALLO-647 as part of the immunosuppressive regimen and remove the antibody from its pipeline entirely. The company will now focus on using only fludarabine and cyclophosphamide (FC) as lymphodepletion treatments for patients receiving cema-cel.

William Blair analysts, while calling the patient mortality "highly unfortunate," 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.

Market Impact and Future Outlook

The news of the patient death and subsequent pipeline adjustment led to a 12% drop in Allogene's stock price during Friday's trading. Despite this setback, analysts remain cautiously optimistic about the company's prospects.

William Blair noted that patients enrolled in ALPHA3 have lower burdens of disease, suggesting that an enhanced lymphodepletion regimen may not be necessary. Furthermore, they speculated that moving forward with just the FC regimen could potentially lead to higher commercial uptake for cema-cel, if approved, given the lower safety risks.

Allogene expects to conduct a futility analysis for the ALPHA3 trial in the first half of 2026, which will provide further insights into the viability of cema-cel as a treatment for large B-cell lymphoma.