#ASCO21: Novartis gears up for CAR-T fight with Gilead in follicular lymphoma — safety may be crucial

 Since winning the first CAR-T approval in the US back in 2017, Novartis has been hard at work expanding the reach of its blockbuster cancer drug Kymriah. Gilead’s Yescarta beat it to the punch in follicular lymphoma (FL) back in March — but now, Novartis says it has new pivotal data that could give its old rival a run for its money.

Of 94 patients given Kymriah for relapsed or refractory FL, 86% responded, according to primary results released ahead of ASCO 2021. A total of 66% saw a complete response — which is just a bit higher than the 65% Novartis touted upon sharing interim results from the Phase II ELARA trial back in December.

These new efficacy results include nearly twice as many patients as the interim analysis, Novartis said. The overall response rate also saw a small bump, up from the 83% rate recorded in December. Median duration of response, progression free survival, and overall survival were not yet reached, according to Novartis.

Despite some familiar efficacy figures, Kymriah could set itself apart on the safety front. No patients experienced Grade 3 or 4 cytokine release syndrome, a well-documented side effect of CAR-T therapy. Those results top Yescarta’s ZUMA-5 data, which showed Grade 3 or higher CRS in 8% of patients.

Grade 1 or 2 CRS occurred in 49% of patients in ELARA, with 9% of patients experiencing Grade 1 or 2 neurological events. One patient experienced Grade 4 neurological events, but recovered. Three participants died from progressive disease, though none of the deaths were treatment-related, according to the Swiss pharma.

Novartis plans on running the new data to regulators “as quickly as possible,” according to Stefan Hendriks, the global head of Novartis Oncology’s cell and gene division. He confirmed in an email to Endpoints News that a submission for the new indication will come sometime this year.

FL is the second most common form of non-Hodgkin lymphoma, with a five-year survival rate of only 20% for patients in the third line and later. Patients with FL have malignant tumors that grow slowly and can become more aggressive over time, and efficacy of available treatments drops off rapidly in later lines. Patients in ELARA had a median of four prior treatments, though some had taken as many as 13.

Yescarta won approval as a third-line therapy back in March, becoming the first CAR-T approved for relapsed/refractory FL. The OK was based on results from the ZUMA-5 trial, in which 91% of patients saw a response, 60% of whom achieved a complete remission, according to Gilead. Median duration of response had not been reached.

“As you know, direct cross trial comparisons are methodically and statistically not appropriate due to differences in patient characteristics, efficacy outcome measures (timing) and in-patient vs. out-patient setting,” Hendriks said in an email. “Head-to-head studies have not been performed, and no comparison of safety and efficacy can be made.”

While Kymriah beat Yescarta out the gate back in 2017, Yescarta has the upper hand in sales, at least in Q1 of this year. The Gilead drug pulled in $160 million last quarter, while Kymriah made Novartis $151 million.

https://endpts.com/asco21-novartis-gears-up-for-car-t-fight-with-gilead-in-follicular-lymphoma-and-safety-could-define-the-battle/