FDA Grants Accelerated Approval to BMS's Zenbexus (iberdomide) as the First-Ever CELMoD for Multiple Myeloma
On August 13, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Bristol Myers Squibb's Zenbexus (iberdomide) in combination with daratumumab, hyaluronidase-fihj, and dexamethasone (a regimen termed ZDd) for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent (IMiD).
Zenbexus is a landmark therapeutic milestone:
- First-in-Class CELMoD: It is the first FDA-approved cereblon E3 ligase modulator (CELMoD), introducing a potent, oral, novel drug class of targeted protein degraders (TPD) to the myeloma therapeutic landscape.
- First Approval Based on MRD-Negativity: This decision marks the first-ever FDA approval in relapsed or refractory multiple myeloma based on a minimal residual disease (MRD)-negative complete response (CR) endpoint. MRD-negativity represents one of the deepest possible measures of clinical response in multiple myeloma and is strongly predictive of improved progression-free survival (PFS).
This approval validates BMS's targeted protein degradation platform and sets the stage for the company's second CELMoD therapy, mezigdomide, which is currently under FDA review.
Efficacy and Trial Data
The accelerated approval was based on results from the Phase III EXCALIBER-RRMM trial:
- Deep Clinical Responses: At a median follow-up of 16 months, the ZDd triplet (n=207) doubled the MRD-negative CR rate compared to the standard-of-care comparator DVd (daratumumab, bortezomib, and dexamethasone; n=213), achieving 41% vs. 21% (p < 0.0001).
- Unblinded Efficacy Data: To preserve the integrity of the study while other endpoints mature, the MRD-negative CR data were first disclosed at the time of approval. The trial remains ongoing, with patients continuing to be evaluated for progression-free survival (PFS), which is the trial's dual primary endpoint.
- Safety Profile: Zenbexus carries boxed warnings for embryo-fetal toxicity (requiring a restricted REMS program) and serious venous and arterial thromboembolism. Severe neutropenia and serious infections (occurring in 40% of patients) are also noted warnings.