FDA Approves Bristol Myers’ Breyanzi for Follicular Lymphoma

Bristol Myers Squibb’s CAR-T therapy, Breyanzi, has received expanded approval from the FDA for treating another type of blood cancer: relapsed or refractory follicular lymphoma (FL) after at least two prior treatments. This broadened approval comes as a significant milestone, nearly three years after Gilead Sciences’ Yescarta became the first CD19-targeted CAR-T therapy for FL, followed by Novartis’ Kymriah, which received the same third-line nod a year later. All three therapies received accelerated approvals based on tumor shrinkage data.

The approval for Breyanzi was driven by promising results from the phase 2 TRANSCEND FL trial. According to the drug's current label, the tumor response rate for patients treated with Breyanzi was 95.7%, with a complete response rate of 73.4%. Although this complete response rate is lower than the 94.1% rate previously reported from the study’s primary analysis, the median duration of response has not yet been reached. Remarkably, 77.1% of responders remain in remission at 18 months.

Comparatively, Gilead’s Yescarta and Novartis’ Kymriah have shown overall response rates of 91% and 86%, respectively, in their third-line FL trials. Their complete response rates stood at 60% and 61%, respectively. Recently, the FDA also approved BeiGene’s BTK inhibitor Brukinsa, in combination with Roche’s anti-CD20 antibody Gazyva, for third-line FL. This combination therapy achieved a 69% response rate, including complete responses in 39% of patients. While the efficacy of Brukinsa and Gazyva appears lower than CAR-T therapies, the advantage lies in its off-the-shelf availability, as opposed to the individualized cell therapies that require weeks of manufacturing.

Following the new accelerated approval, BMS is obligated to provide the FDA with confirmatory evidence to substantiate Breyanzi’s clinical benefits. In March, BMS initiated a phase 3 trial, TRANSFORM FL, which aims to compare Breyanzi against a standard combination treatment in FL patients with one to three previous lines of therapy. This study has an estimated primary completion date of October 2031.

Concurrently, Gilead’s Kite Pharma is conducting the phase 3 ZUMA-22 trial for Yescarta in patients who have undergone at least one prior systemic therapy. This trial began in September 2022 and is projected to reach primary completion in 2030. Both of these CAR-T studies are using progression-free survival as their primary endpoint.

In the broader landscape, Breyanzi and Yescarta are also competing in second-line large B-cell lymphoma. Breyanzi generated $107 million in global sales during the first quarter, consistent with its $101 million total from the last three months of 2023. Comparatively, Yescarta, the leader in the CD19 class, achieved $380 million in global sales in the same period.

To overcome infrastructure challenges in the U.S., Gilead is expanding its network of designated treatment centers and partnering with community practices to ease the treatment process for CAR-T therapies. Meanwhile, Breyanzi is still in the process of expanding its list of approved indications. In March, the FDA approved Breyanzi for previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. The agency is also expected to decide on an application for mantle cell lymphoma by the end of May. These new indications, including FL, are projected to approximately double Breyanzi’s market, as highlighted by BMS’ Chief Commercialization Officer, Adam Lenkowsky, during the company’s first-quarter earnings call in April.