ASH18: Bluebird’s anti-BCMA has a ‘clear lead’ in a crowded field

red blood cells
(Pixabay/Geralt)

This year’s ASH saw a plethora of presentations on BCMA-targeting drugs, but analysts at Jefferies say Bluebird Bio’s CAR-T therapy bb2121 “is still leading the pack.”

The action-packed conference saw trial results for more than 10 anti-BCMA regimens based on autologous CAR-T, off-the-shelf or allogeneic CAR-T, bispecific antibodies and antibody-drug conjugates, making it a particularly overcrowded field.

That said, bb2121’s 95.5% objective response rate (ORR) at the highest dose level—plus its median progression-free survival of 12 months—"sets it apart from other competitors on both efficacy performance and development progress at this juncture,” according to Jefferies.

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While there is still much to learn about Bluebird’s follow-up anti-BCMA CAR-T bb21217, which aims to improve the durability of response, the initial response data are encouraging, as are indications that it is more likely to generate a memory T-cell effect. Taken together, the two programs suggest Bluebird is “well positioned” to target heavily pretreated relapsed and refractory myeloma patients as well as high-risk early/frontline patients.

That’s not to say there won’t be a role for other approaches. Amgen’s bispecific antibodies AMG 420 and longer-acting follow-up AMG 701 are “still in the game” and could be attractive options in some treatment settings “due to their potential advantage in pricing and immediate access if efficacy turns out comparable to bb2121.”

Amgen reported preliminary data on AMG 420 patients at ASH, revealing that seven of 10 heavily pretreated, relapsed or refractory myeloma subjects who received a 400-mg dose responded to the drug, four of whom had minimal residual disease.

Meanwhile, other BCMA-targeting CAR-Ts had mixed fortunes. Jefferies views the results with Poseida Therapeutics’ P-BCMA-01 as “inferior” (43% ORR) at the lower dose of 456 million cells tested. Raising the dose to 845 million cells improved the ORR to 100%, but it looks like the dose is going to have to be higher than those of its rivals.

For comparison, Celgene and Juno’s JCARH125 had an ORR of 83% in patients receiving 150 million cells or more, while at the lowest 50 million dose it still managed 79% ORR.

There were also interesting updates at ASH on anti-CD19 CAR-T approaches, and Jefferies highlighted Allogene’s off-the-shelf product UCART19, which could help cut the waiting times and high production costs associated with harvesting, modifying and reinfusing cells into patients with autologous CAR-T.

An optimized conditioning regimen based on chemotherapy and anti-CD52 antibody alemtuzumab—which is used to clear a path for allogeneic CAR-T cells to exert their effects—proved to be critical. In a trial of UCART19 in acute lymphoblastic leukemia, the overall complete response rate was 82% in 17 patients receiving alemtuzumab plus chemo but dipped to 67% when the whole cohort, including four on chemo alone, was included.