FDA approves Zenbexus, first oral drug in a new class for multiple myeloma

The FDA on Thursday approved Zenbexus (iberdomide) for adults with multiple myeloma, a blood cancer of plasma cells, who have already been through at least one round of treatment. The approval is the U.S. debut of a new drug class for this cancer: cereblon E3 ligase modulators, or CELMoDs, which target the same protein-destruction machinery as the older immunomodulatory drugs (lenalidomide, pomalidomide) but are designed to work in cells that have grown resistant to those earlier medicines.

Zenbexus is taken by mouth, paired with Darzalex (daratumumab), an established antibody drug, and dexamethasone, a steroid long used in myeloma regimens. The triplet is approved for patients whose disease has come back or persisted after at least one prior therapy.

The decision is also the first FDA clearance to use a more sensitive measure of remission as the regulatory endpoint, a signal of how the agency may weigh benefit in future blood-cancer drug development, though the specific endpoint is not named in the announcement.

Peer-reviewed work on iberdomide describes the underlying mechanism. Bristol Myers Squibb Chief Medical Officer Cristian Massacesi framed the approval as opening combination opportunities across the class.

What remains unknown: how durable the responses are, and how Zenbexus will stack up against the next CELMoD in development, mezigdomide.