With US approval at long last for Bristol Myers Squibb’s liso-cel, lymphoma doctors can make a direct comparison of FDA-curated data for the three anti-CD19 Car-T therapies now available. The good news for Bristol is that the agency broadly agrees with the safety and efficacy cited in the most recent cut of liso-cel’s pivotal Transcend study. Thus liso-cel, now branded Breyanzi, has efficacy on a par with Gilead’s Yescarta, with more durable responses and distinctly less cytokine release and neurotoxicity. This at least backs claims made by the product’s originator, Juno, that Breyanzi’s defined 50/50 CD4+/CD8+ T-cell ratio gives a more controllable and safer therapy. This is where the good news ends, however: hospital staff are becoming increasingly expert at handling such toxicities, and a defined-cell product is more expensive to manufacture than one generated from bulk cells. Margins on Car-T therapy are already vanishingly small, and whether Bristol can ever make Breyanzi profitable is a key unknown. And Friday’s approval is cold comfort for funds that had held contingent value rights related to Bristol’s Celgene acquisition: Breyanzi approval not having come by December 31, 2020, the security had already expired.
Comparison of CD19-directed Car-T therapy for DLBCL | |||
---|---|---|---|
Product | Yescarta | Kymriah | Breyanzi |
Company | Gilead | Novartis | BMS |
Black box | CRS & neurotox | CRS & neurotox | CRS & neurotox |
Patients evaluable | 101 (108 for safety) | 68 (106 for safety) | 192 (268 for safety) |
ORR | 72% (51% CR) | 50% (32% CR) | 73% (54% CR) |
mDOR | 9.2 mth | Not evaluable | 16.7 mth |
CRS | 94% (13% ≥gr3) | 74% (23% ≥gr3) | 46% (4% ≥gr3) |
Neurotoxicity | 87% (≥gr3 not given) | 58% (18% ≥gr3) | 35% (12% ≥gr3) |
Source: US product labels. |