FDA Accepts Bristol Myers Squibb's Iberdomide NDA for Multiple Myeloma, Testing New Regulatory Flexibility
核心洞察
Bristol Myers Squibb (搜索) announced FDA acceptance of its New Drug Application for iberdomide, a novel CELMoD agent, combined with daratumumab and dexamethasone for relapsed or refractory multiple myeloma (搜索).
The FDA granted Breakthrough Therapy Designation and Priority Review with a PDUFA date of August 17, 2026, positioning iberdomide as a potential first-in-class CELMoD therapy.
The filing tests FDA's new regulatory flexibility by relying on minimal residual disease (MRD) negativity data from the Phase 3 EXCALIBER-RRMM trial, with progression-free survival data still immature.
Bristol Myers Squibb (搜索) announced that the U.S. Food and Drug Administration (搜索) has accepted a New Drug Application for iberdomide combined with daratumumab and dexamethasone (IberDd) for patients with relapsed or refractory multiple myeloma (搜索) (RRMM). The FDA granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) date of August 17, 2026, marking a significant regulatory milestone for this investigational cereblon (搜索) E3 ligase modulator (CELMoD) agent.
Breakthrough Therapy Designation and Regulatory Innovation
The FDA granted Breakthrough Therapy Designation for iberdomide based on data from the Phase 3 EXCALIBER-RRMM study. Notably, the filing represents a test of the FDA's recently highlighted flexibility regarding multiple myeloma (搜索) study endpoints, as it relies primarily on minimal residual disease (MRD) negativity data while progression-free survival (PFS) data remains immature.
"The FDA's acceptance of this application is a testament to the potential of iberdomide, in combination with anti-CD38 (搜索) monoclonal antibodies, as a novel, potent, oral treatment option, with a manageable safety profile, for patients with multiple myeloma (搜索)," said Cristian Massacesi, executive vice president and chief medical officer at Bristol Myers Squibb (搜索).
The review is being conducted under the FDA's Project Orbis initiative, enabling concurrent review by health authorities in several other countries.
First-in-Class CELMoD Potential
Iberdomide has the potential to become the first approved CELMoD agent, representing a new class of medicines that function as protein degraders targeting Ikaros (搜索) and Aiolos (搜索). This positions the drug as a possible successor to the now off-patent Revlimid, leveraging Bristol Myers Squibb (搜索)'s expertise in targeted protein degradation developed over more than two decades.
The company is the only organization that has successfully developed and commercialized protein degrader agents for multiple myeloma (搜索) treatment. These agents, known as immunomodulatory drugs (IMiDs), helped establish the current standard of care for this incurable disease.
EXCALIBER-RRMM Trial Design and Endpoints
The filing was based on results from a planned analysis of MRD negativity rates in the Phase 3 EXCALIBER-RRMM study (NCT04975997). This multicenter, two-stage, randomized, open-label study evaluated iberdomide in combination with daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with RRMM.
The study assessed dual-primary endpoints of minimal residual disease negativity and progression-free survival, with additional secondary endpoints including overall survival, overall response rate, duration of response, time to progression, time to next treatment, and health-related quality of life. Stage 1 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.
MRD as a Regulatory Endpoint
The acceptance of iberdomide's filing demonstrates the FDA's commitment to its recent guidance backing MRD negativity as an endpoint in relatively early lines of therapy. MRD refers to small numbers of cancer (搜索) cells that may remain after treatment and are undetectable using conventional diagnostic methods.
Modern MRD detection methods, such as next-generation sequencing and next-generation flow cytometry, can identify one malignant cell among 100,000 to 1,000,000 normal cells. MRD negativity may predict improved clinical outcomes, including longer remission and survival, and is increasingly being used in clinical trials as a surrogate endpoint for progression-free survival.
Broader Regulatory Testing
Bristol Myers Squibb (搜索)'s iberdomide filing joins other companies testing the FDA's flexibility on MRD negativity, including AstraZeneca with AZD0120 and Regeneron with Lynozyfic. This regulatory approach could accelerate therapeutic development in multiple myeloma (搜索), where patients face limited treatment options despite current standards of care.
The EXCALIBER-RRMM trial remains ongoing, with patients continuing to be evaluated for progression-free survival. While the trial has been toplined as positive for MRD negativity, no actual data have been published beyond the regulatory filing.