Novartis’ stellar CAR-T efficacy data steamrolls safety doubts to power landmark cancer therapy toward approval 

Novartis HQ
The committee's support for CTL019 puts Novartis' CAR-T on the path to FDA approval.

Novartis’ landmark CAR-T cancer therapy has won the unanimous support of the FDA’s advisory committee. The clean sweep followed a meeting in which CTL019’s stellar efficacy data outshone concerns about safety and manufacturing, setting Novartis up to win the first FDA CAR-T approval by October 3.

Novartis entered the meeting holding the trump card of an 83% complete remission rate, a figure that blows that achieved by existing treatments for kids with B-cell acute lymphoblastic leukemia out of the water. But the novelty of its approach to engineering patients’ own white blood cells to treat cancer left scope for the Swiss Big Pharma to face a rocky ride when the panel probed the production and safety of CTL019.

On the day, a well-drilled Novartis team breezed through the questions to win a 10-0 vote.

The panel discussed neurotoxicity, cytokine release syndrome, the risk of secondary malignancies and the safety implications of the low proportion of CAR-positive T cells in some batches. Many of these issues will need close monitoring if, as expected, Novartis and, a little later, Kite Pharma bring CAR-T therapies to market. And some of the concerns provide opportunities for members of the chasing pack such as Juno Therapeutics and its defined cell composition product and Cellectis and its off-the-shelf candidate to muscle in on the market at a later date.    

None of the concerns were serious enough to derail CTL019, though. 

“I don’t think any of these considerations would be showstoppers for the outstanding clinical results,” City of Hope’s Larry Kwak, M.D., Ph.D., said.

Novartis preemptively defused potential concerns about the long-term safety of CTL019 with a risk mitigation strategy that will establish a 15-year postapproval patient registry. The Big Pharma will provide physicians with a management algorithm to help spot and control toxicities. And it is staggering the rollout of CTL019 to mitigate the risk of its novelty and complexity causing safety problems. Novartis is initially gearing up about 30 sites to administer CTL019. If this goes well, Novartis may add more sites to ensure more patients can access CTL019 without traveling far.

The logistical challenge and cost of getting cells out of a patient, through processing and back into the same individual fast enough to improve outcomes will occupy Novartis and its rivals as they seek to turn personalized therapies into commercial successes. But for now the teams at the University of Pennsylvania and Novartis’ now-defunct Cell and Gene Therapy Unit that developed CTL019 can celebrate bringing a truly novel, highly effective drug to the cusp of approval.

Novartis’ success in managing concerns about manufacturing and safety suggest future FDA panels will look favorably on similarly well handled submissions by its rivals. That translated into small gains in the share prices of Kite and Juno—both rose 0.5% to 1.1% on the day and after hours—but the much larger Novartis was the big winner. Shares in the Big Pharma rose 1.5% on the day.

Kite is the next up. The FDA is due to make a decision on its CAR-T by November 29. Kite CEO Arie Belldegrun, M.D., marked the Novartis advisory committee meeting with a blog post celebrating the progress of the CAR-T field as a whole.

“I will be Novartis’ biggest cheerleader today,” Belldegrun said.