Cellectis reopens the off-the-shelf CAR-T treatment

It is not easy to always keep in mind the very real dangers that CAR-T treatment has it to patients after both Novartis and Gilead granted approvals  successfully supported by impressive data, and with Juno Therapeutics's newly posted possible best-in-class data in a recent trial.

The lesson though is in Juno Therapeutics’ previous CAR-T candidate, the one tested before its most recent promising Phase 2 results. The prior candidate JRA015 had resulted in the deaths of three patients causing a halt to be called on the trial, days later the FDA gave the company permission to begin again – only for another two individuals to suffer serious problems and to die as a result of the treatment.

This would explain why the FDA is being very cautious with how Cellectis manages its reopened Phase 1 clinical trial testing its UCART123 treatment. Working with the FDA, Cellectis announced five stipulations that the company will follow in order to begin the trial again:

Decrease of the cohort dose level to 6.25x104 UCART123 cells/kg
Decrease of the cyclophosphamide dose of the lympho-depleting regimen to 750 mg/m²/day over three days with a maximum daily dose of 1.33 grams of cyclophosphamide
Inclusion of specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, no organ dysfunction since eligibility screening
Provision to ensure that the next three patients to be treated in each protocol will be under the age of 65
Provision to ensure that the enrolment will be staggered across the UCART123 protocols AML123 and ABC123: at least 28 days should elapse between the enrolments of two patients across the two studies
The fourth point seems to have been included to ensure that the company avoids repeating the scenario that led to the death of a 78-year-old man in the first stage of the trial; questions were raised regarding the wisdom of trialling a patient of such an age at such an early stage of clinical trials.

There is some hope that a CAR-T treatment that can avoid the autologous therapy required to extract a patients’ T cells in order to manufacture the therapy could drastically reduce the cost.

In Cellectis treatment, the T cells are donor-derived rather than taken from individual patients – allowing for a much faster production of the therapy.

Shares in the company spiked initially on the release of the news, before settling at 30 cents higher than before the announcement.