- The Food and Drug Administration has paused a Phase 2 trial of a cell therapy Arcellx is developing for multiple myeloma following the death of a study volunteer, the company said Monday. However, patients nearing infusion of the treatment — a personalized CAR-T therapy made from their immune cells — can receive their dose, Arcellx said.
- The company believes “limitations on bridging therapy” — the chemotherapy or other drugs used to keep cancer at bay while awaiting a CAR-T infusion — were a “contributing factor” to the patient death. Executives are seeking changes to the study’s protocol to allow bridging therapies that are “consistent with current clinical practice,” the company said in its statement.
- Gilead Sciences paid $225 million in cash and made a $100 million investment in Arcellx last year to gain rights to the treatment. If successful, Arcellx’s drug could help Gilead compete with other drugmakers with marketed CAR-T therapies for multiple myeloma.
CAR-T treatments are known for their ability to trigger deep durable responses in people with advanced leukemia, lymphoma and more recently, multiple myeloma. But patients typically have to wait days or weeks to get treated while the therapy is being prepared for use, a critical time in which they’re vulnerable to becoming sicker.
“Bridging therapies” like chemotherapy, radiation and immunotherapies are used during this window to help keep patients’ disease in check, and nearly all patients receive it. However, if a study’s design only allows participants to receive drugs they’ve gotten in the past and progressed on, bridging therapy might be less effective, according to a recently published clinical handbook on CAR-T.
In Arcellx’s case, a study participant undergoing bridging therapy progressed to an aggressive form of multiple myeloma called plasma cell leukemia, SVB Securities analyst Daina Graybosch wrote in a research note on Tuesday. Patients with that form of the disease aren’t eligible for Arcellx’s trial, Graybosch wrote after speaking with Arcellx management.
After treatment with Arcellx’s drug, the patient experienced an immune reaction commonly associated with cell therapies and known as cytokine release syndrome. In this case, though, the patient may not have been treated aggressively enough by the site investigator, Graybosch wrote.
While Graybosch believes the FDA will clear Arcellx to resume testing, she questioned whether the regulator will allow for more aggressive bridging therapies in the future, because those therapies could make it harder to tell how well the CAR-T treatment is working.
RBC Capital Markets analyst Brian Abrahams, who covers Gilead, wrote that the trial suspension “may not be a showstopper” for Arcellx because it can be resolved with the FDA. However, the delay won’t help the partners “close the potentially three-year gap” with Legend Biotech, which with partner Johnson & Johnson launched the multiple myeloma CAR-T Carvykti last year.
J&J reported $72 million in Carvykti sales in the first quarter of 2023. Bristol Myers Squibb posted $147 million in sales in the same period for a multiple myeloma CAR-T called Abecma it developed with 2Seventy Bio.
Shares of Arcellx were down 8% in Tuesday trading.