Novartis turned up at ASH with 6-month data for their pioneering CAR-T Kymriah that puts them on the inside track to a quick and near-certain approval for a second indication to treat DLBCL — and straight into a commercial showdown with Gilead/Kite.
Already snagged as the first indication to be OK’d for Gilead/Kite’s Yescarta, Novartis’ investigators nailed down remarkably similar efficacy data at the 6-month mark that closely mirrors their rival. But even with the matching outcomes on efficacy, Novartis’ team still feels that they have a clear marketing edge on the safety front.
Don’t expect an aggressive Gilead, though, to shy from the marketing confrontation that’s about to loom. Their CAR-T was the first to get out from on DLBCL, and the Kite team updated their data today to reflect some outstanding evidence of durability, which will encourage everyone developing CAR-T therapies. (More on that, below.)
The Novartis researchers tracked a slide in results for the 3-month mark, but started at somewhat higher levels than Gilead/Kite that left them side-by-side.
Here’s their comparison, with the standard caveat that scientists hate it when analysts line p data from different studies.
At six months from infusion, the ORR for Kymriah was 37% with a complete response rate of 30%. The median duration of response was not reached. At three months the interim overall response rate discussed at ASCO hit 45% among 23 of 51 patients evaluated with an impressive 37% achieving a complete response and 8% achieving a partial response.
For Gilead/Kite: At 6 months, the ORR in diffuse large B-cell lymphoma (DLBCL) hit 36%, down three points from month three. The CR rate was 31%, down two points.
“Most of the drop-off are the partial responders, in CRs there’s a very small drop off,” says David Lebwohl, an SVP and Novartis’ franchise global program chief.
Lebwohl also highlighted a 73.5% relapse-free rate. The median PFS rate was not yet established.
Where Lebewohl and his colleagues believe they can draw a more distinct difference with the competition is on the safety profile. To be sure, Kymriah wasn’t free of adverse events. Close to one in four experienced grade 3 or 4 cytokine release syndrome. And 12% had a grade 3 or 4 episode involving neurotoxicity. However, no one died and they managed the AEs.
Novartis is also getting its hands on the manufacturing issues that prevented 11 patients from being treated, with a 97% success rate for the last 30 patients. That’s crucial if Novartis expects to successfully go up against the Kite time.
I asked Lebwohl and Pascal Touchon, SVP, global head cell and gene, about their vein-to-vein times, the turnaround that marks the amount of time that a manufacturer takes from the time cells are extracted from patients to the time it takes to infuse them back in.
The biotech, bought out by Gilead for $12 billion, had drilled that down to 17 days, with plans to shave a few more days off.
Novartis, though, doesn’t like the “vein-to-vein” standard. With cryopreservation after apheresis the big pharma prefers to track the time from receipt of cells to their return, giving physicians flexibility on timing re-infusion. How that plays with patients anxious to be treated, though, has yet to be seen.
Now let’s switch back to Gilead and Yescarta.
To evaluate the durability of Yescarta responses, their research team completed an updated analysis on more than 100 patients in ZUMA-1 who had been followed for a minimum of one year. The bottom line:
In this updated analysis, 82 percent of patients had responded to Yescarta, including 58 percent of patients who had achieved complete remission. At a median of 15.4 months post-infusion, 42 percent of patients remained in response, including 40 percent in complete remission. The median duration of response was 11.1 months (95 percent CI: 3.9 months to not estimable [NE]); in patients who have achieved a complete remission, the median duration of response was not reached (95 percent CI: NE). Median overall survival had not been reached (95 percent CI: 12 months to NE) with an overall survival rate at 18 months of 52 percent (95 percent CI: 41 to 62).
That qualifies as another major step forward.
Look for another virtual snap decision from the FDA for Novartis. The agency is hurrying along followup indication decisions, particularly on their spotlight breakthrough programs. And Lebwohl says Novartis is ready to roll, once the green light hits.
The best place to read Endpoints News? In your inbox.
Comprehensive daily news report for those who discover, develop, and market drugs. Join 35,200+ biopharma pros who read Endpoints News by email every day.Free Subscription