FDA advisory committee recommends (10-0) approval of CTL 019 (tisagenlecleucel) CAR-T therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia.-Novartis

Novartis announced that the FDA Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of CTL 019 (tisagenlecleucel), an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).

Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US. Effective treatment options for patients with r/r ALL are limited. In pediatric and young adult patients with B-cell ALL that have relapsed multiple times or become refractory to treatment, the five-year disease-free survival is less than 10-30%].

The ODAC recommendation is based on review of the CTL 019 r/r B-cell ALL development program, which includes the Novartis-led ELIANA study (NCT02435849), the first pediatric global CAR-T cell therapy registration trial. Findings from a US multicenter trial and a single site trial examining the safety and efficacy of CTL 019 among pediatric and young adult patients with r/r B-cell ALL also supported the recommendation and the Biologics License Application (BLA).

CTL 019 was first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL 019 after it is infused into the patient, which may be associated with long-lasting remissions in patients. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including CTL 019, for the investigational treatment of cancers. Children's Hospital of Philadelphia (CHOP) was the first institution to investigate CTL019 in the treatment of pediatric patients and led the single site trial.

Comment: This will be the first chimeric antigen receptor T cell (CAR-T) therapy to reach the market. CTL 019 is a living drug developed by extracting patients' cells, re-engineering them to target CD19 to fight cancer and re-infusing them back into the patient.