The FDA has cleared Breyanzi to treat newly relapsed or refractory large B-cell lymphoma, less than three months after Yescarta became the first CAR-T to reach the second-line setting. (Bristol Myers Squibb )

Gilead Sciences’ Yescarta didn’t get to celebrate very long as the only CAR-T therapy approved for large B-cell lymphoma following just one line of therapy. On Friday, Bristol Myers Squibb joined the game with an even broader approval.

The FDA has cleared Bristol Myers’ Breyanzi to treat newly relapsed or refractory large B-cell lymphoma (LBCL). The nod comes less than three months after Yescarta became first CAR-T drug to enter the second-line setting and a little over a year after Breyanzi’s original go-ahead as a third-line therapy.

Though slightly later to the second-line market, Breyanzi boasts an advantage covering “the broadest patient eligibility” for primary refractory or relapsed LBCL, Nick Botwood, BMS’ senior vice president of U.S. medical affairs, said in an interview with Fierce Pharma ahead of the approval.

Gilead’s Yescarta is indicated for patients who are refractory to frontline chemoimmunotherapy or who relapse quickly within 12 months. Breyanzi’s new approval covers that patient population and includes a specific line about patients who aren’t considered candidates for stem cell transplants.

In the phase 3 Transform trial that supported the approval, Breyanzi cut the risk of event-free survival by 65.1% compared with standard chemotherapy followed by stem cell transplant. Patients on Breyanzi lived median 10.1 months without disease progression or the need for further treatment, versus 2.3 months for the control group.

By comparison, Yescarta registered a 60.2% reduction on a similar event-free survival measurement in its own phase 3 trial dubbed Zuma-7. The Gilead result boasts a longer median follow-up of more than two years, while BMS’ Transform had only followed patients for a median 6.2 months.

Meanwhile, the FDA sweetened the deal for Breyanzi by carving out patients who aren’t considered candidates for stem cell transplants and loosening the eligibility requirement. There, Breyanzi is allowed for patients with refractory disease or who relapse after frontline treatment, regardless of time to relapse.

The broader label comes as a bit of a surprise given BMS only mentioned the Transform trial when Breyanzi nabbed an FDA priority review in February.

Both Yescarta’s Zuma-7 and Breyanzi’s Transform enrolled patients who were fit for stem cell transplant. But BMS apparently added to its application results from the phase 2 Pilot study conducted in transplant-ineligible patients. The company just made the data public a few days ago at the 2022 American Society of Clinical Oncology annual meeting.

In Pilot, 80% of second-line LBCL patients responded to Breyanzi and 54% achieved a complete response after a median follow-up of 12.3 months. Among the responders, the response lasted a median 12.1 months at 15.5 months median follow-up.

Up to 40% of LBCL patients have disease that is refractory to or that relapses after initial therapy, and half of them are not suitable to receive stem cell transplants because of age or underlying diseases, according to BMS estimates.

BMS has estimated the U.S. population of primary relapsed or refractory LBCL is around 14,000 patients. Counting on the CD19-targeting CAR-T therapy to reach other blood cancer settings, the company has said Breyanzi could reach over $3 billion sales by 2029.

Getting an FDA approval only marks the first step in Breyanzi’s second-line journey, and despite the narrow time gap between Breyanzi and Yescarta in this specific indication, Gilead is still ahead of BMS on several fronts given its multi-year head start in the CAR-T game.

For one thing, Yescarta’s second-line DLBCL use has already been added to the National Comprehensive Cancer Network’s guidelines with a category 1—the highest—recommendation. Breyanzi doesn’t have that partly because the Transform results haven’t been published in a peer-reviewed journal.

BMS has submitted for NCCN consideration and will have peer-reviewed publication filed soon, Botwood said. Backing from NCCN is important for reimbursement discussions.

On the manufacturing front, since BMS’ duo cell therapy launches last year, the New York pharma has suffered a production bottleneck for BCMA-targeted CAR-T therapy Abecma. The second-line LBCL use is expected to significantly boost demand for Breyanzi, raising the question of whether the company can make enough supply.

“Based on the progress that we’re making, we are confident that our capacity will expand toward the end of 2022 to meet the needs of these patients,” Botwood said.

Cell therapy production requires a complex process to produce, including drawing a patient’s own blood, genetic modification and expansion of T cells before infusion back to the patient. On the turnaround-time metric, Gilead’s drug also has the edge.

Yescarta boasted a median time of 16 days from blood draw to final product release, according to Gilead data as of the end of 2020. In contrast, Breyanzi’s product turnaround time ranges between 24 days and 33 days, depending on the manufacturing site, Botwood said.

“We’re really committed to consistently and reliably delivering on our goals, and in addition, we’re extremely focused on continuous improvements around investing in efficiencies and optimization to lower the turnaround time without sacrificing quality or safety,” the BMS exec said.

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