In 2017, Novartis’ Kymriah became the first CAR-T therapy approved by the FDA with a go-ahead in acute lymphoblastic leukemia. For the following years, its close rival, Gilead Sciences’ Kite Pharma, didn’t enter the field, but that may soon change.
Gilead’s now positioning its newer CAR-T drug Tecartus for adult acute lymphoblastic leukemia (ALL) with phase 2 data showing the anti-CD19 cell therapy could clear cancer in previously treated patients.
Tecartus wiped out signs of cancer completely in 71% of 55 patients in the phase 2 portion of the ZUMA-3 trial, with the response lasting a median 12.8 months, according to data unveiled at the American Society of Clinical Oncology annual meeting.
With that data, the FDA has put Kite’s filing for Tecartus in ALL under priority review, with a target decision date set for October 1. An approval would expand the use of Tecartus from its current label in relapsed or refractory mantle cell lymphoma.
Tecartus achieved the results in a heavily pretreated population; 47% of patients had previously tried but failed at least three other therapies before the CAR-T.
Previous research has linked prior use of Amgen’s CD3-CD19 bispecific T-cell engager Blincyto to a reduced response to a CD19-directed CAR-T. Among 25 ZUMA-3 patients who had previously received Blincyto, the complete remission rate for Tecartus stood at 60%.
Frank Neumann, M.D., Ph.D., Kite’s newly-minted global head of clinical development, labeled the showing as “outstanding” for the ALL field. Patients still need to be followed longer to produce long-term response data, he noted during an interview ahead of the presentation. The current data were calculated after a median follow-up of 16.4 months.
CAR-T therapies are known to come with the dangerous side effect of cytokine release syndrome, and Tecartus is no exception. In ZUMA-3, 24% of patients experienced immune overreaction at grade 3 or above and 25% had neurologic events at those levels. Two patients’ deaths were linked to the treatment, including one brain herniation and one septic shock.
Neumann said Tecartus’ safety profile here was comparable to prior experience and the side effects were mostly manageable and acceptable for this heavily pretreated patient population.
In its own clinical trial in relapsed or refractory ALL, Kymriah recorded a complete remission rate of 83% three months after infusion, and 49% of patients experienced cytokine release syndrome of grade 3 or above.
Kymriah’s Eliana trial and Tecartus’ ZUMA-3 trial tested the two CAR-T drugs in different ALL populations. Kymriah is currently allowed for use in children and young adults up to 25 years of age, while Tecartus targets only the adult population. This gives them a small overlap if Tecartus is eventually approved. Overall, about four out of every 10 cases of ALL are in adults, according to the American Cancer Society.
Gilead currently has two marketed CAR-T therapies, both targeting the CD19 antigen. In the first quarter, the older Yescarta brought in sales of $160 million, and Tecartus hauled in $31 million. Novartis’ Kymriah returned $151 million during the same period.