ROCKET TRIAL DEATHS

Juno deaths: Toxicity is therapy specific, not risk to whole CAR-T field, say experts

By Dani Bancroft contact

- Last updated on GMT

iStock/Movus
iStock/Movus

Related tags: Immune system

The deaths in a trial of Juno Therapeutics’ JCAR015 are most likely product-specific says the CEO of French CAR-T developer TxCell, who rejected the idea that chemotherapy or the CD19 target played a part.

Earlier this week there were two additional deaths​ in the Juno Therapeutics ROCKET trial for relapsed/refractory acute lymphoblastic leukemia (ALL).

This meant the death toll increased from four in July to six last week, despite excluding the chemotherapy drug fludarabine from the trial.

Juno originally suspected that fludarabine and cyclophosphamide given in combination with the JCAR015 therapy was the cause of the adverse effects, and after a temporary clinical hold​ the US FDA agreed to allow the trial to resume.

Biopharma-Reporter contacted another company working in the space; French immunotherapy specialist TxCell to discuss the wider implications.

TxCell uses different immunotherapeutic approaches to that of Juno, but has an extensive team of experts from the CAR-T field.

Stephane Boissel, CEO of TxCell told us that “it doesn’t seem to be the preconditioning regimen [fludarabine],”​ and he suspects that there is “some kind of problem with the specific CAR-T product [JCAR015]”​.

CD19 target

Given other experimental therapies also target the T-cell receptor CD19, firms like Kite Pharma, Novartis or Cellectis trials haven’t seen the same significant level​ of brain swelling in their trials.

Boissel therefore added he’s also “not sure if the [adverse events] have anything to do with the target CD19 at all.”

However, CAR-T has always had the risk of cytokine release syndrome (CRS). As Boissel explained “most symptoms you see with CAR-T are linked to overstimulation of the immune system.”

But combatting CRS is what many biotechs have been working on to prevent​.

Boissel added - “Of course, with the whole approach there are reactions, but generally not this level of toxicity.”

Alternative approaches

TxCell is working on cell therapies​ with the same principle as CAR-T, but instead target chronic diseases such as Crohn’s or uveitis - inflammatory diseases of the gut and eye.

Boissel added their CAR-Treg technology is “not targeting the same antigen -  not even going the same kind of antigen.” ​TxCell also targets a smaller number of cells, but to help stop inflammation of tissues instead of killing cancer cells.

TxCell therefore has no plans to pursue any oncology indications using CAR-Tregs, and Boissel reiterated, “[Cancer] is not our expertise”.

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