PRINCETON, N.J., August 14, 2026

Bristol Myers Squibb announced that the U.S. Food and Drug Administration has granted accelerated approval to ZENBEXUS™ (iberdomide) in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. The approval is based on results from the Phase 3 EXCALIBER-RRMM trial, where the ZENBEXUS combination achieved a 41% minimal residual disease-negative complete response rate, compared with 21% for the daratumumab, bortezomib and dexamethasone comparator regimen. The approval makes ZENBEXUS the first FDA-approved cereblon E3 ligase modulator (CELMoD), representing a new class of targeted protein degradation therapies for multiple myeloma.

ZENBEXUS Demonstrates Deeper Responses in Relapsed Myeloma

In the Phase 3 EXCALIBER-RRMM study, the ZENBEXUS-based regimen demonstrated a statistically significant improvement in MRD-negative complete response, one of the study’s dual primary endpoints. At a median follow-up of 16 months, 41% of patients receiving ZENBEXUS plus daratumumab, hyaluronidase-fihj and dexamethasone achieved MRD-negative complete response, compared with 21% receiving daratumumab, bortezomib and dexamethasone. MRD negativity represents one of the deepest measures of treatment response in multiple myeloma and is increasingly used to assess the depth of disease control. The EXCALIBER-RRMM study remains ongoing to evaluate progression-free survival, while additional clinical data are expected later in 2026. The accelerated approval is contingent upon verification and description of clinical benefit in confirmatory trial results.

First FDA-Approved CELMoD Marks New Treatment Class

ZENBEXUS is designed to build on Bristol Myers Squibb’s long-standing expertise in targeted protein degradation and cereblon biology. CELMoDs are engineered to modulate the cereblon E3 ubiquitin ligase complex and promote degradation of selected proteins involved in disease biology. The company is evaluating ZENBEXUS across additional treatment settings, including the EXCALIBER Maintenance study, as it seeks to expand the potential role of the therapy in multiple myeloma. However, the treatment also carries important safety risks. In the EXCALIBER-RRMM study, serious infections and neutropenia were prominent adverse events, while venous and arterial thromboembolic events were also reported. The product carries boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolism and is available through a restricted distribution program.

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ZENBEXUS Approval Strengthens Protein Degradation Pipeline

The FDA decision represents a significant milestone for Bristol Myers Squibb’s protein degradation platform and the broader development of targeted degraders in oncology. The company is advancing multiple protein-degradation approaches, including CELMoDs, ligand-directed degraders and degrader antibody conjugates, with the goal of addressing disease-driving proteins that have historically been difficult to target. Another investigational CELMoD, mezigdomide, is also under FDA review in combination with carfilzomib and dexamethasone, with a PDUFA target date of May 13, 2027. For ZENBEXUS, the current accelerated approval is based specifically on MRD-negative complete response, making the ongoing evaluation of progression-free survival particularly important. The approval provides a new treatment option for eligible patients with relapsed or refractory multiple myeloma while establishing CELMoDs as an emerging therapeutic class in hematologic oncology.

Source: Bristol Myers Squibb,press release