ASH: Bristol Myers bolsters Breyanzi's case in earlier lymphoma amid clash with Gilead

When Bristol Myers Squibb originally unveiled pivotal data for Breyanzi in second-line large B-cell lymphoma (LBCL) a year ago, a key weak point was a short follow-up time in the study. Now, the New York pharma is cranking up its CAR-T rivalry against Gilead Sciences with updated results.

Breyanzi’s ability to keep LBCL in check remained strong over a longer period in the phase 3 TRANSFORM trial. After a median follow-up of 17.5 months, Breyanzi cut the risk of tumor nonresponse, disease progression or death by 64.4% compared with a standard of care involving stem cell transplant.

The results, shared at the American Society of Hematology 2022 annual meeting, almost matched the 65.1% risk reduction Breyanzi registered during an interim analysis of TRANSFORM, which was performed at 6.2 months of median follow-up.

The new results also look similar to what Gilead’s rival CAR-T therapy Yescarta posted last year. After a median follow-up of more than two years, the ZUMA-7 trial showed Yescarta pared down the same risk by 60.2%.

For Breyanzi, the BMS drug also eradicated signs of cancer in more patients than control therapy did. At the longer follow-up, Breyanzi posted a complete response rate of 74% versus 43% for the control arm.

The more mature data establish Breyanzi as a new standard of care option for second-line LBCL, Anne Kerber, BMS’ head of cell therapy development, said in an interview with Fierce Pharma ahead of the data presentation.

While the latest Breyanzi follow-up was still shorter than Yescarta’s, Kerber said she doesn’t believe that matters.

“There is no ambiguity in there,” Kerber said, pointing to large, consistent improvements across all trial endpoints. 

Breyanzi also showed promise in prolonging patient lives, although its 27.6% reduction in the risk of death didn’t meet statistical significance. Investigators estimated that 73.1% of patients would still be alive in the Breyanzi arm at 18 months, versus 60.6% in the control group.

The TRANSFORM trial wasn’t designed to show a statistically significant survival benefit, Kerber said. But she noted the data demonstrated a “clinically relevant difference” because the survival curves between the two treatment arms separated “very nicely.”

Targeting a “very efficient sample size,” BMS only enrolled 92 patients in each treatment arm to avoid randomizing a large number of patients to existing standard of care, Kerber explained. The trial therefore wasn’t powered for an overall survival analysis. In addition, 67% patients in the control arm actually went on to receive Breyanzi after disease progression.

While clinical data suggest Breyanzi could put up a fight against Yescarta, several factors are currently holding the BMS drug back from reaching its full commercial potential despite it boasting a broader label than Yescarta.

In a recent interview with Mizuho, Ran Reshef, M.D., leader of Columbia University Medical Center’s cell therapy program, said he likes both Breyanzi and Yescarta based on their efficacy. But he views Yescarta as having an edge because of better manufacturing success and consistent turnaround time, according to a Mizuho note published Monday.

By comparison, BMS reported issues with its Breyanzi manufacturing success rate in the third quarter. While the company said the underlying issue has been resolved and that it expects the rate to improve, doctors’ perceptions of the product could take time to rebound.

Meanwhile, BMS has been struggling to meet demand for its CAR-T therapies. Back in July, BMS pushed back its timeline to have increased Breyanzi supply to early next year.

“Delivering that capacity is a top priority,” BMS Chief Commercial Officer Chris Boerner, Ph.D., said during a conference call in July. He noted that the company’s focus is on increasing both vector supply and drug production slot availability.

In a statement to Fierce Pharma, a BMS spokesperson said the company has been encouraged by “a steady increase” in Breyanzi’s manufacturing capacity, pointing to a new approved suite for producing viral vectors, a key component to deliver cell therapies. BMS current has cell therapy facilities in Warren and Summit, New Jersey, along with Bothell, Washington. One new facility in Devens, Massachusetts, is expected to come online in 2023, as is one in the Netherlands in 2025.