FDA has approved Zenbexus (iberdomide) in combination with daratumumab and hyaluronidase-fihj and dexamethasone, a regimen the company refers to as ZDd, for adult patients with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.

Full approval for this indication will be contingent upon verification and description of clinical benefit in confirmatory trials. Zenbexus is contraindicated in females who are pregnant.¹

The approval marks the arrival of a new drug class in multiple myeloma. Zenbexus is the first FDA-approved CELMoD, a designation for a group of therapies known as cereblon-modulating protein degraders.¹ The drug carries boxed warnings for embryo-fetal toxicity and venous and arterial thromboembolism. "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," said Cristian Massacesi, MD, chief medical officer and head of development at Bristol Myers Squibb. "As the first approved CELMoD, Zenbexus marks the arrival of a new treatment class and is an important milestone in our efforts to expand what is possible for patients with multiple myeloma. And we believe this is only the beginning. 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."

What was the approval based on?

Approval of Zenbexus was based on results from the Phase III Excaliber-RRMM trial, which evaluated ZDd against daratumumab, bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma.² At a median follow-up of 16 months, ZDd demonstrated a statistically significant improvement in one of the trial's dual primary endpoints: minimal residual disease-negative complete response occurred in 41% of patients treated with ZDd, compared with 21% of patients treated with DVd.²

Minimal residual disease negativity is among the deepest measures of response in multiple myeloma and is considered predictive of improved progression-free survival. This decision marks the first FDA approval in relapsed or refractory multiple myeloma based on minimal residual disease-negative complete response.¹

"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," said Sagar Lonial, MD, FACP, FASCO, Excaliber-RRMM lead investigator and chief medical officer of the Winship Cancer Institute of Emory University. "The strong results observed with the CELMoD-based combination within a familiar triplet approach creates the potential for a new treatment foundation in multiple myeloma."

What comes next for Bristol Myers Squibb's pipeline?

Zenbexus is the first FDA-approved CELMoD, but it is not the company's only one in development. A New Drug Application for mezigdomide, an investigational CELMoD, in combination with carfilzomib and dexamethasone is also currently under review with FDA, with a Prescription Drug User Fee Act target date of May 13, 2027.¹

"The goal for every person living with multiple myeloma is not simply to live longer, but to live well," said Heather Cooper Ortner, president and chief executive officer of the International Myeloma Foundation. "That is why it is important to have access to effective therapeutic options, particularly in the community setting where the majority of myeloma care is delivered. This approval represents an important step forward by expanding treatment options for patients facing their first relapse. Every new option gives patients and their healthcare teams additional choices as treatment needs evolve, as well as renewed hope for the future."

Sources

1. U.S. FDA Grants Accelerated Approval to Bristol Myers Squibb's First CELMoD Therapy ZENBEXUS™, in Combination with Daratumumab and Hyaluronidase-fihj and Dexamethasone (ZDd) for Patients with Multiple Myeloma, as Early as First Relapse Bristol Myers Squibb August 13, 2026, https://news.bms.com/news/details/2026/U-S--FDA-Grants-Accelerated-Approval-to-Bristol-Myers-Squibbs-First-CELMoD-Therapy-ZENBEXUS-in-Combination-with-Daratumumab-and-Hyaluronidase-fihj-and-Dexamethasone-ZDd-for-Patients-with-Multiple-Myeloma-as-Early-as-First-Relapse/default.aspx
2. EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma National Library of Medicine Accssesed August 14, 2026, https://pubmed.ncbi.nlm.nih.gov/40346992/