BMS's iberdomide faces Aug. 17 FDA decision on an MRD-based myeloma filing
The NDA rests on an interim MRD-negativity win in EXCALIBER-RRMM while the trial's own progression-free survival data are still maturing.
Executive Summary
- The FDA is due to decide by mid-August on Bristol Myers Squibb's application to add an oral CELMoD agent to a standard daratumumab-based regimen for relapsed or refractory multiple myeloma, built on a Phase 3 trial that has not yet reported its second primary endpoint.
- The filing rests on an interim analysis showing a statistically significant improvement in minimal residual disease negativity, a signal regulators increasingly accept as informative, but one that has not historically stood alone as the sole basis for approval in this disease.
- A Breakthrough Therapy designation attached to the same interim data set signals that regulators found the early signal compelling enough to accelerate review, even as the trial's progression-free survival comparison continues to mature.
- The relapsed/refractory myeloma field is dense with CD38-, BCMA- and CRBN-directed regimens already in Phase 3 or later, so this decision determines whether an oral, cereblon-degrading option joins an already crowded set of combination regimens rather than opening new therapeutic ground.
The filing
The FDA accepted Bristol Myers Squibb's New Drug Application for iberdomide combined with daratumumab and dexamethasone (IberDd) in relapsed or refractory multiple myeloma and set a Prescription Drug User Fee Act target action date of August 17, 2026. The agency also granted Breakthrough Therapy designation for iberdomide based on the same data package. Bristol Myers Squibb's chief medical officer, Cristian Massacesi, called the drug "a novel, potent, oral treatment option, with a manageable safety profile". Review is proceeding under the FDA's Project Orbis initiative, which allows concurrent review by other countries' health authorities. U.SU.S. Food and Drug Administration Accepts Bristol Myers Squibb's New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple MyelomaFeb 17, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial actually showed
The submission is grounded in EXCALIBER-RRMM (NCT04975997), a Phase 3, two-stage, open-label trial that randomized approximately 664 patients in its second stage to IberDd or to daratumumab, bortezomib and dexamethasone (DVd). The study carries dual primary endpoints: minimal residual disease negative complete response and progression-free survival. On September 23, 2025, Bristol Myers Squibb reported that a planned interim analysis showed a statistically significant improvement in MRD negativity rates for IberDd versus DVd, with a safety profile consistent with the known profiles of the components. The trial continues to follow patients for the other primary endpoint, progression-free survival, and for overall survival as a key secondary measure. NCT04975997+1Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)NCT04975997U.S. Food and Drug Administration Accepts Bristol Myers Squibb's New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple MyelomaFeb 17, 2026
Filing ahead of the full readout
The application went in on the MRD result alone, while the co-primary progression-free survival comparison remains open. Minimal residual disease negativity is increasingly used as a surrogate for progression-free survival in myeloma and is gaining regulatory recognition for accelerating development, but it is a surrogate, not the trial's full evidentiary package. The primary completion date for the trial has also moved, most recently from March 2026 to November 2027, alongside enrollment growing from 864 to 939 patients as the trial finalized its analysis population. Neither shift altered the interim MRD result already reported, but it means the confirmatory progression-free survival data BMS's own trial was designed to produce will land after, not before, this month's decision. U.S+1U.S. Food and Drug Administration Accepts Bristol Myers Squibb's New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple MyelomaFeb 17, 2026Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)NCT04975997
The competitive setting
Relapsed or refractory multiple myeloma is a heavily contested indication. The direct comparator field around iberdomide's Cereblon E3 Ubiquitin Ligase Complex mechanism includes CD38-directed daratumumab and isatuximab regimens from Janssen and Sanofi, BCMA- and GPRC5D-directed bispecifics including Regeneron's linvoseltamab and Janssen's teclistamab and talquetamab, and Takeda's ixazomib, all running in Phase 3 or later multiple myeloma trials. Bristol Myers Squibb is separately running a Phase 3 trial of iberdomide as post-transplant maintenance therapy against lenalidomide (NCT05827016), extending the same mechanism into an earlier line of therapy. Against that backdrop, an FDA clearance would not introduce a new mechanism to the field; iberdomide's IKZF1/IKZF3-degrading approach follows established immunomodulatory precedent in myeloma, so the bar this decision sets is whether the combination's MRD advantage over DVd, a currently used triplet regimen, is durable enough to justify a place alongside the CD38 and bispecific options already available to relapsed patients.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.