The U.S. Food and Drug Administration has granted accelerated approval to Zenbexus(iberdomide), Bristol Myers Squibb’s oral cereblon-modulating protein degrader, for use alongside daratumumab and hyaluronidase-fihj and dexamethasone in adults with multiple myeloma who have progressed after at least one earlier treatment that included both a proteasome inhibitor and an immunomodulatory drug.
The clearance introduces an entirely new mechanistic category to myeloma care. Zenbexus is the first agent in the CELMoD class to reach the U.S. market, engineered to more potently degrade the Ikaros and Aiolos transcription factors than earlier immunomodulatory agents, driving tumor cell death alongside immune activation. Company leadership described the milestone as validation of years invested in targeted protein degradation research and a signal of further CELMoD candidates to come.
Support for the approval came from the Phase III EXCALIBER-RRMM trial, which pitted the new triplet against daratumumab, bortezomib and dexamethasone. After roughly 16 months of follow-up, minimal residual disease-negative complete responses were achieved by 41 percent of patients on the Zenbexus regimen versus 21 percent on the comparator arm — the first RRMM approval in the U.S. anchored to this endpoint. The regimen carries boxed warnings for embryo-fetal harm and thromboembolic events and is dispensed only through a restricted safety program; continued marketing will depend on confirmatory survival data.
Investigators involved in the trial noted the combination’s potential to reshape the standard treatment sequence for patients facing their first relapse, while patient advocacy leaders emphasized the value of expanding options available in community oncology settings. Bristol Myers Squibb’s pipeline includes a second CELMoD, mezigdomide, currently under FDA review in combination with carfilzomib and dexamethasone, with a target decision date in May 2027.
Written By: Sayan Das
Graphics by: Pramit Hazra
