Photo from Penn Medicine
CTL019
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the T-cell therapy CTL019 to treat adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL).
The therapy consists of a patient’s own T cells genetically engineered to produce chimeric antigen receptors (CARs) directed against CD19.
CTL019 is the first personalized cellular therapy for cancer to receive breakthrough designation from the FDA.
Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over available therapies.
The breakthrough designation for CTL019 is based on early trial results in adults and children with ALL.
At ASH 2013, researchers presented results of the first 27 ALL patients (22 children and 5 adults) treated with CTL019. Eighty-nine percent of the patients achieved a complete response to the treatment. Six patients relapsed during follow-up, which ranged from 2 months to 18 months.
There was also a high rate of toxicity, particularly cytokine release syndrome, but this was resolved via treatment with the IL-6 agonist tocilizumab.
The first pediatric ALL patient to receive CTL019 celebrated the second anniversary of her cancer remission in May. And the first adult patient remains in remission 1 year after receiving the therapy.
“Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said Carl June, MD, of the University of Pennsylvania.
“Receiving the FDA’s breakthrough designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.”
In August 2012, the University of Pennsylvania announced an exclusive global research and licensing agreement with Novartis to further study, develop, and commercialize personalized CAR T-cell therapies for the treatment of cancers.
Trials of CTL019 began in the summer of 2010 in patients with relapsed and refractory chronic lymphocytic leukemia, and they are now underway for patients with ALL, non-Hodgkin lymphoma, and myeloma.
CTL019 cells are a patients’ own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.
