FDA Grants Accelerated Approval to Bristol Myers Squibb's Zenbexus, the First CELMoD Therapy, for Multiple Myeloma — First Approval Ever Based Directly on MRD Endpoint

The FDA granted accelerated approval to iberdomide (Zenbexus, Bristol Myers Squibb) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone (ZDd) for adults with multiple myeloma who received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. Zenbexus is the first approved cereblon E3 ligase modulator (CELMoD), a new drug class, and the approval is also the first in multiple myeloma history to be granted directly on the basis of minimal residual disease (MRD)-negative complete response as a surrogate endpoint rather than progression-free survival. In the Phase 3 EXCALIBER-RRMM trial (NCT04975997), ZDd achieved a 41% MRD-negative complete response rate versus 21% for the control DVd regimen (p<0.0001) at 16-month median follow-up; PFS data remain immature and are required to confirm the accelerated approval. Safety signals include high rates of neutropenia (90.2% all-grade, 84.3% Grade 3-4), infections (78.9%, including 2% fatal), and thromboembolism (9.8%), with 4.9% fatal adverse reactions overall. Because of embryo-fetal toxicity risk, Zenbexus is available only through the restrictive ZENBEXUS REMS program. Analysts project U.S. sales could exceed $1 billion by early 2031.