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Bristol Myers Squibb’s ZENBEXUS Receives FDA Accelerated Approval for Multiple Myeloma
Friday, August 14, 2026
Bristol Myers Squibb has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to ZENBEXUS™ (iberdomide), in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd), for adults with multiple myeloma who have received at least one previous line of treatment, including a proteasome inhibitor and an immunomodulatory agent.
Minimal residual disease refers to the small number of cancer cells that may remain in the body after treatment but cannot be detected using conventional diagnostic methods. In multiple myeloma, MRD testing is increasingly used to measure the depth of a patient’s response to treatment.
ZENBEXUS is the first FDA-approved cereblon E3 ligase modulator (CELMoD), introducing a new class of targeted protein degraders for the treatment of multiple myeloma.
The approval is based on results from the Phase 3 EXCALIBER-RRMM trial, which evaluated ZDd against daratumumab, bortezomib and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma.
At a median follow-up of 16 months, 41% of patients receiving ZDd achieved minimal residual disease (MRD)-negative complete response, compared with 21% of patients receiving DVd. The difference was statistically significant, making this the first FDA approval for relapsed or refractory multiple myeloma based on MRD-negative complete response.
The EXCALIBER-RRMM study enrolled 939 patients who had received one to two previous lines of anti-myeloma therapy. The primary efficacy analysis for MRD negativity included the first 420 patients enrolled in the study. Treatment continued until disease progression or unacceptable toxicity.
The trial is continuing to assess progression-free survival (PFS), which is one of its dual primary endpoints. Further results from the study are expected later this year. Full approval of ZENBEXUS for this indication will depend on confirmation of clinical benefit through ongoing or additional confirmatory trials.
The safety profile of ZDd was consistent with the known effects of the treatment combination. Around 7.8% of patients discontinued ZDd because of adverse reactions.
Neutropenia and infections were among the most frequently reported adverse events, occurring in 90.2% and 78.9% of patients, respectively. Other commonly reported reactions included upper respiratory tract infection, fatigue, musculoskeletal pain, pneumonia, diarrhoea, motor dysfunction, rash, sleep disorders, hypogammaglobulinaemia, COVID-19 and constipation.
Serious adverse reactions included pneumonia, upper respiratory tract infection, second primary malignancies, neutropenia, febrile neutropenia, COVID-19 and sepsis. Fatal adverse reactions were reported in 10 patients receiving ZDd.
The application was reviewed under the FDA’s Project Orbis initiative, which enables concurrent review of oncology treatments by regulatory authorities in participating countries.
Bristol Myers Squibb is also advancing its broader CELMoD development programme. The company’s investigational CELMoD mezigdomide, in combination with carfilzomib and dexamethasone, is currently under FDA review, with a Prescription Drug User Fee Act target date of 13 May 2027.
Source: bms.com
