Novartis' Kymriah flops in earlier lymphoma use, where Gilead, Bristol Myers CAR-T rivals succeeded

Novartis’ Kymriah is losing its shot at a key market expansion opportunity in second-line lymphoma, where CAR-T rivals from Gilead Sciences and Bristol Myers Squibb recently found success.

Kymriah couldn’t outdo standard of care at staving off disease progression or death—or achieving improvements in shrinking tumors—in patients with aggressive B-cell non-Hodgkin lymphoma who have failed on one prior line of treatment, Novartis said Tuesday. The standard treatment is salvage chemotherapy followed by stem cell transplant.

The result, from the phase 3 BELINDA study, marked a jarring failure for Kymriah, which in 2017 became the first CAR-T therapy to win an FDA approval. The drug’s two CD19-directed CAR-T competitors, Gilead’s Yescarta and Bristol Myers’ Breyanzi, both recently posted trial wins in the same second-line lymphoma setting.

As of now, the three CAR-T drugs are battling it out as third-line treatments for diffuse large B-cell lymphoma (DLBCL), a type of aggressive lymphoma. But the companies are eyeing earlier lines of treatment and other indications to expand their markets.

RELATED: Gilead's Kite matches Bristol Myers with Yescarta CAR-T win in earlier lymphoma

In a Tuesday statement, Jeff Legos, Ph.D., Novartis’ head of oncology and hematology development, was quick to separate the second-line flop from Kymriah’s existing indication in the third-line setting. In its approved uses, which include acute lymphoblastic leukemia, Kymriah has shown durable responses and a favorable safety profile in over 5,300 patients, Novartis said.

Still, getting into earlier lines of treatment would open up larger markets for the three drugs. In June, Gilead’s Kite Pharma announced that Yescarta showed a 60.2% improvement in a similar event-free survival endpoint in its own second-line DLBCL phase 3 trial, dubbed ZUMA-7. That marker covers time to disease progression, start of a new drug or death.

Following Gilead’s readout, RBC Capital Markets analyst Brian Abrahams predicted Yescarta’s second-line peak sales would reach $622 million, almost double his estimate for the third-line setting.

RELATED: Bristol Myers' cell therapy Breyanzi, fresh off an FDA nod, eyes earlier lymphoma use with first-in-class win

Yescarta’s results back in June came on the heels of a Bristol Myers win for Breyanzi in the phase 3 TRANSFORM trial—also in DLBCL. But because Bristol Myers hasn’t quantified Breyanzi’s improvement over standard of care, it’s hard to tell a winner between the two drugs.

Yescarta boasts an advantage as the Gilead drug has already been building its presence in the market for years, Abrahams noted. Kymriah and Yescarta were the first CAR-Ts to enter the U.S. market back to back in 2017, and Breyanzi just entered the fray in February.

Plus, Yescarta has longer follow-up data than Breyanzi.

RELATED: ASCO: Positive trial shows Novartis' Kymriah poised to play catch-up in CAR-T rivalry with Gilead's Yescarta

While the second-line B-cell lymphoma use now appears out of reach for Kymriah, the drug remains on track to expand into third-line follicular lymphoma. Data from the ELARA trial showed Kymriah completely cleared signs of cancer in 66% of previously treated patients, and 86% of patients experienced a response, according to results unveiled at the recent American Society of Clinical Oncology annual meeting.

There, Kymriah will still have to compete with Yescarta, which won an FDA nod in March after recording a 91% overall response rate.

Yescarta currently leads the CD19 CAR-T field with $338 million sales in the first half of the year. Kymriah brought in $298 million during the same period.