What happened
Bristol Myers Squibb won FDA accelerated approval for Zenbexus (iberdomide) in combination with Johnson &. Johnson’s Darzalex 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, according to an Aug. 14 Fierce Pharma report that cited an Aug. 13 company statement. Fierce characterized the decision as the first FDA approval for a CELMoD therapy and the first FDA nod for a new drug in multiple myeloma driven directly by minimal residual disease, or MRD, as a surrogate endpoint rather than longer-term measures such as progression-free survival. In the phase 3 Excaliber-RRMM trial, the regimen beat Darzalex, Takeda’s Velcade (bortezomib) and dexamethasone on one of two primary endpoints, posting an MRD-negative complete response rate of 41% versus 21% at any time during a median follow-up of 16 months. The trial is ongoing to assess progression-free survival, which Fierce said is expected this year. Because the approval is accelerated, BMS must provide confirmatory evidence.
Why it matters
The significance is twofold. Bristol Myers Squibb now has the first commercial validation for its CELMoD franchise, which Fierce described as a historic breakthrough for targeted protein degradation. The FDA also has a live precedent for using MRD in myeloma as a regulatory bridge rather than waiting for progression-free survival, with implications for development timelines and trial design. Myeloma sponsors will likely study the decision closely, especially because Fierce said the FDA issued draft guidance in January on the potential use of MRD and complete response to support accelerated approval in myeloma after a unanimous 2024 endorsement from an external advisory committee.
For investors and payers, this remains an accelerated-approval story, not a finished efficacy story. The open item is progression-free survival from Excaliber-RRMM, which remains one of the trial’s dual primary endpoints and is expected this year. If that readout is supportive, Zenbexus could look like both a product launch and a broader regulatory template. If it disappoints, the MRD-based precedent will face tougher scrutiny. Detailed drug monographs are at ClinicalRx.ai. For pricing context, see RxInfo.ai.
