Reality Bites for Amgen’s bispecifics

Developing bispecific antibodies is not easy. Just ask Amgen, which last night disclosed the halting of three such projects: pavurutamab because of apparent toxicity, AMG 673 because of a target overlap with another asset, and AMG 596 owing to “portfolio prioritisation”. All three are bispecific T-cell engagers (Bites), which are relatively small constructs that retain only some antibody features, as opposed to many other companies’ bispecifics that use a full antibody format. Those competitors have also had their problems, with Regeneron recently revealing US clinical hold on odronextamab after an Ash presentation that revealed much toxicity. True, Amgen is pressing on with the rest of its Bite portfolio, and has not written pavurutamab off. But it has made clear that cytokine release syndrome, a side effect typically associated with Car-T therapy, is also a big problem for bispecifics, on yesterday’s analyst call saying this toxicity was “the single challenge that sits before the entire [bispecifics] field”.