Bristol Myers' Breyanzi bags FDA nod to follow CAR-T rivals Gilead, Novartis into follicular lymphoma

The FDA has broadened the use of Bristol Myers Squibb’s CAR-T therapy Breyanzi to another type of blood cancer.

Breyanzi has won an accelerated approval to treat patients with relapsed or refractory follicular lymphoma (FL) after at least two prior lines of therapy.

Wednesday’s nod came about three years after Gilead Sciences’ Yescarta became the first CD19-targeted CAR-T therapy to enter FL. Novartis’ Kymriah followed about a year later with the same third-line nod. All three meds secured accelerated approvals based on tumor shrinkage data.

BMS' Breyanzi won over the FDA thanks to results from the phase 2 TRANSCEND FL trial. The drug’s current label shows a tumor response rate of 95.7% for patients who received the CAR-T therapy, including a 73.4% rate for complete responses. The complete response figure was notably smaller than the 94.1% rate reported last June from the study’s primary analysis.

The median duration of response has not been reached for Breyanzi, with 77.1% of responders still in remission at 18 months.

By comparison, Gilead’s Yescarta and Novartis’ Kymriah have posted overall response rates of 91% and 86%, respectively, in third-line FL in their separate trials. Their complete response rates were 60% and 61%, respectively.

Meanwhile, the FDA a few weeks ago greenlighted BeiGene’s BTK inhibitor Brukinsa, used together with Roche’s anti-CD20 antibody Gazyva, for third-line FL. The combo triggered a response in 69% of patients, including complete responses in 39% of them.

Although the efficacy power of Brukinsa and Gazyva appeared to be weaker than the CAR-T therapies, the regimen offers an off-the-shelf option, whereas the individualized cell therapies require weeks of manufacturing before reaching the patient.

With the new accelerated approval, BMS is on the hook to provide the FDA with confirmatory evidence to support Breyanzi’s clinical benefit in this use. In March, the New Jersey pharma registered a phase 3 trial coded TRANSFORM FL, which is designed to pit Breyanzi against the investigator’s choice of a standard combination treatment in FL patients who have received one to three prior lines of therapy. The study bears an estimated primary completion date of October 2031.

In the meantime, Gilead’s Kite Pharma is running the phase 3 ZUMA-22 trial for Yescarta, also in patients who have tried at least one prior line of systemic therapy. The trial kicked off in September 2022 and currently bears a primary completion date in 2030. Both CAR-T studies use progression-free survival as their primary endpoint.

Elsewhere, Bristol's Breyanzi and Gilead's Yescarta are currently duking it out in second-line large B-cell lymphoma. As a CD19 latecomer, Breyanzi generated $107 million worldwide in the first quarter, which was about flat compared with its $101 million total from the last three months of 2023. As the CD19 class leader, Yescarta brought in $380 million in global sales in the first quarter of this year.

To expand the reach of its cell therapies, Gilead is working through a CAR-T infrastructure bottleneck in the U.S. by expanding the number of designated treatment centers and by partnering with community practices to facilitate treatment.

As for Breyanzi, the BMS drug is still in the process of building out its list of approved indications. The FDA in March approved Breyanzi for previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma, and the agency is slated to decide by the end of May an application in mantle cell lymphoma. These new indications, including FL, together will roughly double Breyanzi’s addressable market, BMS’ chief commercialization officer, Adam Lenkowsky, said during the company’s first-quarter earnings call in April.