Bristol Myers Squibb Secures Landmark FDA Accelerated Approval for Zenbexus (Iberdomide), the First-Ever CELMoD
On August 13, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Bristol Myers Squibb's (BMS) ZENBEXUS (iberdomide), marking a historic regulatory milestone as the first-ever approved cereblon E3 ligase modulator (CELMoD). Belonging to a new class of oral cereblon-modulating protein degraders, Zenbexus represents a major commercial and scientific breakthrough for the targeted protein degradation (TPD) field.
Zenbexus was approved in combination with daratumumab/hyaluronidase-fihj (Darzalex Faspro) and dexamethasone (a regimen referred to as ZDd or IberDd) for the treatment of adult patients 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).
A Regulatory First: Approval Based on MRD-Negative Complete Response
In addition to introducing a new drug class, this decision marks the first-ever FDA approval in relapsed or refractory multiple myeloma based on minimal residual disease (MRD)-negative complete response (CR) as a surrogate endpoint.
The approval is supported by efficacy results from the Phase 3 EXCALIBER-RRMM trial, which randomized patients to receive either the ZDd combination (n=207) or a standard control regimen of daratumumab, bortezomib, and dexamethasone (DVd; n=213):
- At a median follow-up of 16 months, the ZDd regimen demonstrated a highly statistically significant improvement in the dual primary endpoint of MRD-negative CR, achieving a 41% response rate (n=85; 95% CI: 34-48) compared to 21% (n=44; 95% CI: 15-27) in the DVd control arm (p < 0.0001).
- MRD-negativity is considered one of the deepest measures of clinical response in multiple myeloma and is highly predictive of improved progression-free survival (PFS).
Safety and Regulatory Contingencies
Because Zenbexus was cleared under the accelerated approval pathway, its continued approval is contingent upon the verification and description of clinical benefit in confirmatory trials. Efficacy will be further evaluated using PFS, which serves as the other dual primary endpoint of the ongoing EXCALIBER-RRMM trial.
Zenbexus carries a Boxed Warning regarding:
- Embryo-fetal toxicity: Due to its structural and mechanistic relationship to thalidomide-analogue immunomodulatory agents, Zenbexus can cause severe birth defects or embryo-fetal death. It is available only through a restricted distribution program called the ZENBEXUS REMS.
- Venous and arterial thromboembolism: Patients are at increased risk of deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke, requiring prophylactic antithrombotic therapy.
Verbatim Quotes
From Dr. Cristian Massacesi, Chief Medical Officer and Head of Development at Bristol Myers Squibb, on August 13, 2026:
"Today’s approval of ZENBEXUS represents meaningful progress for patients living with multiple myeloma and underscores the power of our targeted protein degradation platform, particularly our CELMoD programs. This approval validates years of scientific research and strengthens our confidence in the potential of this approach as we continue to advance our innovative pipeline on behalf of patients with significant unmet needs."
From Dr. Sagar Lonial, lead investigator of the EXCALIBER-RRMM trial and Chief Medical Officer of the Winship Cancer Institute of Emory University:
"The FDA approval of iberdomide marks the anticipated arrival of a new therapeutic class for relapsed or refractory multiple myeloma and has the potential to make a meaningful difference for patients."