New Approval Sets Up CAR-T Showdown for Gilead, Novartis

Kymriah now indicated for relapsed or refractory diffuse large B cell lymphoma

Kymriah (tisagenlecleucel), the landmark cell therapy Novartis brought to market last year, has gained a new indication that puts it in direct competition with Yescarta (axicabtagene ciloleucel), a rival treatment from Gilead Sciences, according to a recent BioPharma Dive article.

Both therapies now hold FDA approvals for adults with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Kymriah's original approval was for patients younger than 25 years of age who have relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

During a first quarter earnings call in April, CEO of Novartis Oncology Liz Bennett said the company had 35 sites established for Kymriah infusion and that the company was working to expand in preparation for the DLBCL patients.

Gilead's Yescarta didn't get much time on the DLBCL market before Novartis came knocking with its own CAR-T therapy. Gilead, though, may hold the upper hand in this head-to-head matchup, the article said.

As EP Vantage's Jacob Plieth points out, the FDA calculated Kymriah’s efficacy using less than half of the patients enrolled in the pivotal study that led to the therapy's approval. Of the 161 patients in the intent-to-treat population, 49 never received infusions for various reasons (death, manufacturing failure, physician's call, etc.). Another 24 patients who did get infusions were left out of the efficacy determination because it was inconclusive whether they had DLBCL.

What's more, Yescarta's label carries noticeably better response rates in DLBCL than Kymriah's. For example, on overall response rate (ORR) the FDA cites 72% for Gilead's therapy and 50% for the Novartis drug. Given the labeling differences, Novartis may face competitive challenges for its new indication.

The potential headwinds don't seem to be disheartening the Swiss pharma giant. Barrett noted on the April earnings call that Novartis hasn't seen any problems with Kymriah reimbursement, the article reports.

"We expect that we'll see the trajectory improve over time but again, keeping in mind, not only with ALL but also as DLBCL outlet starts to launch, that these patients need to be referred to the centers," Barrett said on the earnings call last month, adding that she thinks there will be "continuous improvement quarter-over-quarter, but you will see it. It will take time for these centers to get up and running and used to using this new therapy."

Some have speculated CAR-T manufacturers would set indication-specific list prices for their drugs, which Novartis did in setting a $373,000 list price for Kymriah in DLBCL—matching Yescarta's list price. For the original ALL indication, Kymriah's wholesale acquisition cost clocked in at $475,000.

Kymriah fetched $12 million during the first quarter, while Yescarta scored $40 million, beating consensus estimates.

Source: BioPharma Dive; May 2, 2018.