ASH18: Amgen’s anti-BCMA bispecific shines again, but CAR-T threat remains

amgen
Amgen presented data on AMG 420 alongside an update on the progress of its anti-CD33 bispecific. (Amgen)

Amgen has posted early clinical data on anti-BCMA T cell engager AMG 420 in patients with relapsed or refractory multiple myeloma. The 70% objective response rate and lasting efficacy at the optimum dose show the drug has promise, but time-consuming administration via continuous infusion and the presence of CAR-T competitors cast a shadow over its prospects.

AMG 420 has the same bispecific T cell engager design as Amgen’s pioneering antibody Blincyto. In the case of AMG 420, one arm binds to T cell antigen CD3 while the other latches onto tumor antigen BCMA to facilitate immune attacks on the cancer cells. The big question has been whether the attack will have the targeted ferocity of anti-BCMA CAR-Ts in development at bluebird bio and elsewhere.

Amgen, which licensed AMG 420 from Boehringer in 2016, provided an early answer to that question in September when it revealed all five subjects in the highest dose arm of its multiple myeloma trial had complete responses. 

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Now, Amgen has followed up with more data at the annual meeting of the American Society of Hematology. The latest snapshot shows seven of the 10 heavily pretreated relapsed or refractory subjects who received 400mg dose responded to the drug. Four of the subjects had minimal residual disease negative complete responses, meaning no cancer cells were found in their bone marrow.

Coupled with a lack of major toxicities seen up to 400mg, the data paint AMG 420 as a highly effective option for patients with relapsed or refractory multiple myeloma. And as an off-the-shelf bispecific, AMG 420 an edge over rival autologous anti-BCMA CAR-T therapies as it can be used immediately.

Less upbeat readings of Amgen’s prospects are possible, though. A significant minority of patients suffered serious infections. And each cycle of AMG 420 consisted of four weeks of continuous infusion, meaning the multi-cycle treatment programs used in the trial placed significant burdens on patients. 

Amgen is advancing a follow-up asset, AMG 701, that has a longer half life. But, while AMG 701 may be less burdensome for patients, it remains unclear whether the impressive efficacy of the bispecifics will be enough to compete with CAR-T therapies. The most advanced anti-BCMA CAR-T, bluebird and Celgene’s bb2121, achieved an 81% response rate in an even more heavily pretreated population than that enrolled in Amgen’s trial. Notably, most of bluebird’s patients had tried Darzalex.

Amgen presented data on AMG 420 alongside an update on the progress of its anti-CD33 bispecific, AMG 330. Efficacy data on AMG 330 are more preliminary, but Amgen still chalked up a couple of complete responses that offers some encouragement for future readouts. 

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