FDA Accepts BMS’s NDA for Iberdomide in RRMM

Bristol Myers Squibb announced that the U.S. FDA has accepted its New Drug Application (NDA) for iberdomide combined with daratumumab and dexamethasone (IberDd) to treat relapsed or refractory multiple myeloma (RRMM).

This filing marks a potential advance for patients with this incurable blood cancer, with a Prescription Drug User Fee Act (PDUFA) target action date of August 17, 2026.

Iberdomide belongs to a novel class of cereblon E3 ligase modulator (CELMoD) agents, part of Bristol Myers Squibb’s targeted protein degradation (TPD) platform. These oral drugs work by tagging disease-causing proteins for destruction inside cells, targeting “undruggable” proteins that traditional inhibitors can’t touch.

Building on BMS’s legacy with immunomodulatory drugs (IMiDs) like Revlimid, CELMoDs aim to deliver potent, manageable treatments for hard-to-treat cancers.

Breakthrough Data from EXCALIBER-RRMM Trial Drives Filing

The NDA stems from a planned interim analysis of the Phase 3 EXCALIBER-RRMM study (NCT04975997), a randomized trial pitting IberDd against daratumumab, bortezomib, and dexamethasone (DVd) in about 664 RRMM patients. Notably, the filing used minimal residual disease (MRD) negativity rates as a key endpoint a bold move highlighting MRD’s rising role in oncology.

Understanding MRD’s Role in Modern Myeloma Trials

MRD measures tiny remnants of cancer cells post-treatment, undetectable by standard tests. Using sensitive tools like next-generation sequencing (NGS) or flow cytometry, it spots one malignant cell among 100,000 to 1 million normal ones. MRD negativity predicts longer remission and survival, serving as a surrogate for progression-free survival (PFS).

The trial’s dual primary endpoints are MRD negativity and PFS, with secondaries like overall survival (OS) and response rates still under evaluation.

Stage 1 confirmed 1.0 mg iberdomide as the optimal dose based on safety, pharmacokinetics, and efficacy. The FDA granted Breakthrough Therapy designation based on these MRD data, fast-tracking review under Project Orbis for concurrent global assessments.

What This Means for Multiple Myeloma Patients

RRMM patients often cycle through therapies as the disease resists standard options. IberDd offers a novel oral regimen with anti-CD38 daratumumab, potentially improving efficacy and convenience.

 “This acceptance underscores iberdomide’s potential as a potent, oral option with a manageable safety profile,” said Cristian Massacesi, BMS executive vice president and chief medical officer.

BMS credits patients and investigators in the ongoing EXCALIBER study. If approved, iberdomide could expand TPD’s impact, joining BMS’s pipeline of degraders like ligand-directed degraders (LDDs) and degrader antibody conjugates (DACs) across oncology and beyond.

This milestone signals accelerating innovation in myeloma care, where MRD endpoints could reshape regulatory paths.

Reference

U.S. Food and Drug Administration Accepts Bristol Myers Squibb’s New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma, 17 February 2026, Bristol Myers Squibb – U.S. Food and Drug Administration Accepts Bristol Myers Squibb’s New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma

Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM), ClinicalTrials.gov ID NCT04975997, https://clinicaltrials.gov/study/NCT04975997

Lonial S et al, EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma. Future Oncol. 2025 Jun;21(14):1761-1769. Epub 2025 May 10. PMID: 40346992; PMCID: PMC12150652. https://doi.org/10.1080/14796694.2025.2501920