Pharma major Bristol Myers Squibb (BMS) has received US regulatory approval for iberdomide (Zenbexus), the first cereblon E3 ubiquitin ligase modulator (CELMoD) to reach the market, for use in combination with daratumumab and dexamethasone in adults with multiple myeloma (MM) who have received at least one prior line of therapy.

The approval rests on the Phase III EXCALIBER-RRMM trial, which compared iberdomide plus daratumumab-dexamethasone against daratumumab-bortezomib-dexamethasone in relapsed or refractory disease. At a median 16-month follow-up, the iberdomide arm achieved a minimal residual disease (MRD)-negative complete response rate (CRR) of 41% versus 21% for control, marking the first time US regulators have approved a relapsed or refractory myeloma therapy primarily on an MRD-negative CRR endpoint.

Iberdomide's differentiation lies in its next-generation cereblon pharmacology, offering greater degradation potency than lenalidomide and pomalidomide against transcriptional regulators Ikaros and Aiolos, whilst fitting into an all-oral, steroid-light backbone.