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

Existing CD19-directed CAR-T therapies are all reserved for certain large B-cell lymphoma patients who’ve tried at least two prior therapies. But Bristol Myers Squibb, the latest player to join the field, is eying earlier treatment thanks to a first-in-class clinical win.

Compared with gold-standard treatment, Bristol Myers’ Breyanzi helped more patients clear tumors or stave off disease worsening in a phase 3 trial, the company said Thursday. The improvement on the so-called event-free survival marker in large B-cell lymphoma (LBCL) patients who had failed on one initial therapy and who were eligible for stem cell transplant was “clinically meaningful and statistically significant,” the company added.

The trial marks the first time a CD19-directed CAR-T therapy proved its worth in second-line LBCL, and the first time any therapy has topped standard-of-care combinations of Roche’s Rituxan and high-dose chemotherapy, followed by stem cell transplant, in relapsed or refractory LBCL, Bristol Myers noted.

The event-free survival marker encompasses death, disease progression, failure to achieve complete or partial remission, and initiation of new therapies out of efficacy concerns. Breyanzi also outperformed standard of care on key secondary endpoints, including at completely eradicating signs of cancer and prolonging the time before tumor progression.

Data on how well Breyanzi could extend patients’ lives were immature at this interim analysis, BMS said. No new safety concerns arose from the trial.

RELATED: Bristol Myers' Breyanzi tunes its pitch for fight against entrenched CAR-T players Novartis and Gilead

Thanks to an FDA go-ahead in February, Breyanzi can now compete against rival CAR-T therapies from Novartis and Gilead Sciences to treat LBCL patients after two or more lines of systemic therapy. With the latest result, BMS said it’s going to share the data from the phase 3 Transform trial with regulators in hopes of moving up one line in the treatment sequence.

Last August, MorphoSys and Incyte’s antibody drug Monjuvi, used in tandem with Bristol Myers’ Revlimid, became the first drug specifically approved by the FDA to treat second-line diffuse large B-cell lymphoma. But that green light was based on cancer shrinkage data from a single-arm trial without a comparator.

RELATED: ASH: Gilead's CAR-T med Yescarta shows promise earlier in lymphoma therapy

Breyanzi may have some CAR-T company in earlier LBCL soon. Gilead’s Kite Pharma is conducting the phase 3 Zuma-7 trial, pitting Yescarta as a second-line treatment for DLBCL against standard of care. That study was launched about a year ahead of Breyanzi’s Transform trial but enrolled nearly twice as many patients.

Breyanzi is obviously late to the CD19 CAR-T field, but BMS hopes its safety profile could differentiate itself from Kymriah and Yescarta, which have built up years of marketing experience.

Meanwhile, BMS is currently facing investor pushback around the delayed approval of Breyanzi. Holders of the contingency value rights tied to the New York pharma’s acquisition of Celgene are suing the company for failing to do its best in securing a timely nod for the drug. Because BMS missed an approval deadline, Celgene shareholders missed out on a $6.4 billion payout.