- Novartis' CAR-T hopeful CTL019 looks to be broadly as effective in lymphoma as rival Kite Pharma's experimental cell therapy axi-cel, according to study results released Wednesday.
- At three months, 45% of the 51 patients evaluated to date from Novartis' JULIET study saw a response to treatment with CTL019. More than a third, 37%, achieved a complete response — data roughly on par with the efficacy seen from Kite's axi-cel at the same time mark, although cross-trial comparisons should be taken cautiously.
- Shares in Kite rallied more than 8% on the news, perhaps reflecting investor relief that Novartis' candidate did not dramatically outperform Kite's drug. Novartis has already submitted CTL019 for regulatory review in adult lymphoblastic leukemia, with a decision expected as early as September.
Novartis had kept its JULIET data in diffuse large B-cell lymphoma (DLBCL) under wraps, even after it announced the Food and Drug Administration had granted CTL019 a Breakthrough Therapy tag in that indication.
The Swiss pharma's announcement of the trial results Wednesday was timed to coincide with the release of an abstract scheduled to be presented at the International Conference on Malignant Lymphoma in Lugano, Switzerland next week.
Treatment with CTL019 led to a best overall response rate (ORR) of 59% among the 51 patients evaluated for analysis, dropping to a 45% ORR at the three-month mark.
Importantly, no deaths or cases of cerebral edema were reported with CTL019. Still, 57% of all treated patients (85) experienced cytokine release syndrome (CRS), a dangerous adverse event commonly seen with CAR-T treatment. Roughly one in four patients experienced Grade 3 or higher CRS, a rate higher than the 13% seen in Kite's six-month update of its ZUMA-1 study.
Thirteen percent of patients receiving CTL019 experienced neurological adverse events, compared to 28% seen with axi-cel in Kite's study.
Novartis only treated 85 of the 141 patients who enrolled in the trial with CTL019, mainly due to patient dropouts from disease progression.
"Of the patients who discontinued the trial before infusion, the majority were due to rapid progression of their disease or deterioration in their clinical status," said Novartis spokesperson Eric Althoff in reply to a request for comment from BioPharma Dive.
Only nine of the 141 enrolled patients discontinued the study as a result of Novartis' inability to manufacture an adequate dose of CTL019, Althoff said. Given the complex nature of producing CAR-T therapy from a patient's own T cells, manufacturing is a key challenge to the development and hoped-for commercialization of the technology.
Novartis estimates its time from the start of manufacturing to product release will be 22 days at launch, if CTL019 is approved by the Food and Drug Administration as expected. That would be about a week slower than the 14-day turnaround Kite Pharma is targeting for its process from receiving a patient's cells to when the engineered T-cells are returned.
Kite has pushed forward with axi-cel in DLBCL and anticipates a decision from the FDA by November 29. With Novartis' anticipated approval in ALL this year and competitive efficacy in DLBCL, the two could quickly come into direct competition in the DLBCL indication.
Juno Therapeutics, which was set back by patient deaths in a study testing its lead CAR-T, is further behind but still a potential player in the space. Data presented at the annual meeting of the American Society for Clinical Oncology this past weekend showed Juno's second-generation CAR-T led to a 39% complete response rate at 3 months in DLBCL, albeit in a smaller number of patients.