CAR-T, FDA

FDA advisers back Novartis’ game-changing personalized CAR-T for cancer, approval in sight

The FDA’s advisory committee on cancer drugs has offered a group thumbs-up for Novartis’ trailblazing CAR-T CTL019 (tisagenlecleucel), marking a key milestone for the pharma giant as it nears the likely launch of a groundbreaking personalized cell therapy for B-cell acute lymphoblastic leukemia.

These outside experts at the FDA voted 10 to 0 to urge an approval for this drug, offering some key support after regulators carefully reviewed the complex manufacturing process as well as the safety and efficacy profiles of this therapy.

Key to Novartis’ success was the high remission rate as well as 6-month and 12-month survival data for children and young adult patients who were running out of options. The patient numbers were small, but the responses were extraordinary for the patients who responded, with an 83% overall remission rate and 79% overall survivability rate at 12 months – hitting the primary endpoint.

“This is a novel therapy, there’s an unmet medical need, a strong efficacy and a good risk mitigation strategy,” noted committee member James Gulley from the National Cancer Institute.

Alan Rein from the Center for Cancer Research cited the drug’s “remarkable clinical successes,” though he noted some lingering concerns with the long-term risks involved. And others echoed those remarks, raising the prospect that CAR-T can be a game-changer in this field.

David Lebwohl

David Lebwohl, Novartis’ chief of the CTL019 program, told the panel earlier in the day that these outcomes were unlike anything he’d seen in 20 years of practice.

But this therapy is also linked with threatening side effects. While patients on this engineered CAR cell therapy have been repeatedly hit by potentially lethal cases of cytokine release syndrome and neurological toxicity with the threat of new malignancies, advisers were clearly willing to accept the risk in order to achieve the potential gains. There were no cases of cerebral edema, investigators noted, but other CAR-Ts have been linked to such cases.

Novartis also noted the death of a patient from a cerebral hemorrhage. Also, 9 patients had to discontinue the trial after CTL019 couldn’t be manufactured for them – a key shortfall that Novartis will have to manage carefully if it gets a green light for manufacturing.

Several of the committee members, though, offered Novartis a vote of confidence on their risk mitigation strategy and the ability of specialists in the field to handle side effects.

The last three years of development work at Novartis has been marked by organizational restructuring along with the advance and retreat of rival therapies – all while sorting through a threatening list of toxicity factors. But Novartis’ team maintained their lead, delivering on a promise Novartis CEO Joe Jimenez made to persist with the development of a dramatic new approach to treating cancer.

Observers crowded into the FDA’s presentation room this morning, rubbing shoulders with CAR-T celebs like Penn’s Carl June with many, many more looking on online. But the review involves more than just one therapy at one company. The advisers gathered at a time that the FDA has committed itself to accelerating the development of major new therapies under new FDA commissioner Scott Gottlieb, and CTL019 will be viewed as a test case for the agency’s openness to new therapies that are not yet thoroughly probed in advanced clinical trials.

The vote also underscores ODAC’s ingrained acceptance of moderate risk when it comes to treating patients dying of cancer.

Close on Novartis’ heels is a team from Kite, a CAR-T-focused biotech which had hoped to be the first to the market. Kite today got a front row seat to the way the agency views these therapies, and it’s likely to take advantage of that in its own upcoming regulatory review.

Behind them comes Juno, with a new lead drug, and a group of players like Cellectis, which are in the early stages of developing what they hope can be off-the-shelf therapies that should be less expensive to make and market.



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