Allogene's first clinical data for off-the-shelf myeloma CAR-T clouded by patient death

Allogene won’t present early clinical data for its off-the-shelf multiple myeloma CAR-T therapy for another month, but a patient death in the phase 1 trial has sent its shares tumbling.

The company’s stock opened Wednesday morning 13% down from the previous day’s close after it shared some numbers it would present at the American Society of Hematology’s (ASH's) virtual meeting in December. Among those numbers were safety results for 17 patients and efficacy data from 15, with a focus on five patients who had received the highest dose of the company’s anti-BCMA CAR-T treatment, ALLO-715.

Before receiving that highest dose—320 million cells—two of the five patients underwent lymphodepletion with Allogene’s antibody ALLO-647, along with cyclophosphamide, a chemo drug also used to suppress the immune system. This treatment is used ahead of CAR-T and other cell therapies to clear a path for them to work. One of the patients saw their tumors shrink, but the other patient died from an infection—a suspected case of fungal pneumonia, the company said in a statement.

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The infection was diagnosed the day after the patient received ALLO-715, and the investigator chalked it up to the cancer worsening and the conditioning regimen. Three other patients reported infections, but they recovered with treatment.

Although the patient death moved Allogene’s stock, infections aren’t unheard of in patients who receive anti-BCMA CAR-T treatments, Jefferies analyst Biren Amin wrote in a note to clients, referring to a separate ASH abstract reporting that about half of patients given this type of CAR-T suffered infections.

Infections affected about one-quarter of the 17 patients in Allogene's study who were evaluated for safety. The most common severe side effects were anemia and neutropenia—an abnormally low white blood cell count—both of which affected 41% of patients.

The other three patients who got the highest dose got a different conditioning regimen, adding the chemo drug fludarabine on top of cyclophosphamide and ALLO-647. The treatment shrank tumors in two patients, banishing them completely in one of them. Despite these responses, the data on the whole were “underwhelming,” JPMorgan analyst Cory Kasimov wrote in a note to clients.

RELATED: ASCO: Allogene reports 63% response rate in early trial of off-the-shelf CAR-T in lymphoma

“Although early, the efficacy looks underwhelming when compared to autologous CAR T therapies,” Kasimov wrote, referring to CAR-T treatments made with a patient’s own cells rather than from donor cells. “[The] Grade 5 death due to infection related to lymphodepletion is concerning,” he added.

Allogene is testing two dose levels, 39 mg and 90 mg, of its antibody ALLO-647, with these data coming from patients who all took the lower dose. The highest dose may work better if its performance in the phase 1/2 study of Allogene’s lymphoma CAR-T is any indication, Jefferies’ Amin wrote. That study tested the treatment ALLO-501 in 22 patients, shrinking tumors in 63% of them and eliminating tumors in 22%.