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Personalized Cell Therapy CTL019 Receives FDA ‘Breakthrough Therapy’ Designation
The FDA has granted “breakthrough therapy” status to CTL019 (Novartis), an investigational chimeric antigen receptor (CAR) therapy for the treatment of pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL).
According to the FDA, a “breakthrough therapy” designation is intended to expedite the development and review of new medications that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. It is a distinct status from both accelerated approval and priority review.
CTL019 uses CAR technology to reprogram a patient’s own T-cells to “hunt” cancer cells that express CD19 proteins. After they have been reprogrammed, the T-cells are re-introduced into the patient’s blood. They then proliferate and bind to the targeted CD19-positive cancer cells, destroying them.
Because CTL019 is an investigational therapy, its safety and efficacy profiles have not been established. Investigational therapies are available only through controlled and monitored clinical trials.
In a study presented at the 55th American Society of Hematology (ASH) annual meeting, held December 7–10, 2013, in New Orleans, 22 pediatric patients with relapsed or refractory ALL received a targeted T-cell dose range of 107 to 108 cells/kg, with a transduction efficiency (TE) of 11% to 45%, and five adult patients received a target dose of 5 × 109 total cells divided over 3 days, with a TE of 6% to 31%.
Nineteen (86%) of the 22 pediatric patients achieved complete remissions (CRs). The first pediatric patient treated with the protocol was still in remission 20 months later. Five pediatric patients relapsed, including one whose tests identified new tumor cells that did not express the CD19 protein targeted by the reprogrammed cells.
In addition, all five of the first adult ALL patients treated with CTL019 experienced CRs, the longest of which continued 6 months after treatment. One adult patient subsequently underwent a bone-marrow transplant and remained in remission. Another adult patient relapsed after 3 months with disease; this patient tested negative for the CD19 protein.
ALL is the most common pediatric cancer, representing approximately 25% of cancer diagnoses among children younger than 15 years of age. ALL also occurs in adults. If not treated, the disease can be fatal within a few months.
Sources: Novartis; July 7, 2014; and Novartis; December 7, 2013.