FDA Accepts Bristol Myers Squibb's Iberdomide Application for Multiple Myeloma

The U.S. Food and Drug Administration has accepted Bristol Myers Squibb's New Drug Application for iberdomide combined with daratumumab and dexamethasone in patients with relapsed or refractory multiple myeloma. The FDA has granted a Prescription Drug User Fee Act (PDUFA) date of August 17, 2026 for this indication.

Iberdomide belongs to a new class of medicines called cereblon E3 ligase modulator (CELMoD) agents and has the potential to become the first approved drug in this category. CELMoD agents are designed to utilize targeted protein degradation (TPD) to address therapeutically relevant proteins.

The FDA has granted both Breakthrough Therapy Designation and Priority Review for this application. The filing was based on results from a planned analysis of minimal residual disease (MRD) negativity rates in the Phase 3 EXCALIBER-RRMM study evaluating iberdomide as a treatment for relapsed or refractory multiple myeloma patients.

The executive vice president and chief medical officer at Bristol Myers Squibb stated that the FDA's acceptance of this application is a testament to the potential of iberdomide, in combination with anti-CD38 monoclonal antibodies, as a novel, potent, oral treatment option, with a manageable safety profile, for patients with multiple myeloma. The filing for iberdomide based on the MRD endpoint underscores the company's commitment to pioneering new ways of advancing life-saving therapies for patients living with cancer.

The review is being conducted under the FDA's Project Orbis initiative, which enables concurrent review by health authorities in several other countries.

EXCALIBER-RRMM (NCT04975997) is a Phase 3, multicenter, two-stage, randomized, open-label study evaluating the efficacy and safety of iberdomide in combination with daratumumab and dexamethasone (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma. The study is designed to assess dual-primary endpoints of minimal residual disease (MRD) negativity and progression-free survival (PFS), with additional secondary endpoints including overall survival (OS), overall response rate (ORR), duration of response (DoR), time to progression (TTP), time to next treatment (TTNT), and health-related quality of life (HR-QoL).

Stage 1 of the study identified 1.0 mg iberdomide as the optimal dose based on safety, pharmacokinetics, and efficacy data. In Stage 2, approximately 664 patients were randomized to receive either IberDd or DVd. The EXCALIBER-RRMM trial is ongoing and patients continue to be evaluated for progression-free survival.

Minimal residual disease (MRD) refers to the small number of cancer cells that may remain in a patient's body after treatment and are undetectable using conventional diagnostic methods. In multiple myeloma, MRD assessment has emerged as a highly sensitive and clinically meaningful tool for evaluating treatment response. MRD negativity does not necessarily mean all cancer cells are gone, but it may predict improved clinical outcomes, including longer remission and survival.

Modern MRD detection methods, such as next-generation sequencing (NGS) and next-generation flow cytometry (NGF), can identify one malignant cell among 100,000 (threshold for MRD) to 1,000,000 normal cells, offering unprecedented precision in measuring disease burden. MRD is increasingly being used in clinical trials as a surrogate endpoint for progression-free survival (PFS) and is gaining recognition from regulatory authorities for its role in accelerating therapeutic development.

Targeted protein degradation (TPD) is a differentiated research platform at Bristol Myers Squibb built on more than two decades of scientific expertise, providing new avenues to degrade therapeutically relevant proteins that were previously considered "undruggable." Bristol Myers Squibb is the only company that has successfully developed and commercialized protein degrader agents for the treatment of multiple myeloma. These agents, known as immunomodulatory drugs (IMiDs), helped establish the current standard of care in the treatment of this disease, which remains without a cure. Bristol Myers Squibb is building on this foundation with several investigational protein degraders in clinical trials, leveraging three different modalities including CELMoD agents, ligand-directed degraders (LDDs), and degrader antibody conjugates.