Princeton, N.J., September 22, 2025 – Bristol Myers Squibb (BMS) announced that its investigational cereblon E3 ligase modulator (CELMoD™) iberdomide achieved a statistically significant improvement in minimal residual disease (MRD) negativity rates in the Phase 3 EXCALIBER-RRMM trial for patients with relapsed or refractory multiple myeloma (RRMM). The positive outcome emerged from a planned interim analysis and paves the way for a potential new standard in targeted protein degradation therapies for this difficult-to-treat blood cancer.
The study evaluated iberdomide in combination with daratumumab and dexamethasone (IberDd) versus the standard regimen of daratumumab, bortezomib, and dexamethasone (DVd). Based on the recommendation of the independent Data Monitoring Committee, the trial will continue without changes to assess the co-primary endpoint of progression-free survival (PFS), along with key secondary endpoints including overall survival (OS) and safety. The safety profile of iberdomide was consistent with previous clinical data, reinforcing its potential as a novel therapy for multiple myeloma.
Science Significance
Iberdomide represents the first of a new class of cereblon E3 ligase modulators (CELMoDs) designed to enhance targeted protein degradation, a mechanism that eliminates disease-driving proteins previously considered “undruggable.” By targeting the cereblon E3 ubiquitin ligase complex, iberdomide promotes the degradation of transcription factors essential for myeloma cell survival.
Minimal residual disease (MRD) negativity—indicating the absence of detectable cancer cells using next-generation sequencing or flow cytometry—has emerged as a key biomarker predicting deeper, more durable remissions. Achieving MRD negativity at a statistically significant rate signals a breakthrough in the ability to measure and potentially improve long-term outcomes for RRMM patients.
Regulatory Significance
Bristol Myers Squibb plans to engage with regulatory authorities to discuss the positive MRD data and its implications for accelerated development. MRD negativity is increasingly recognized by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) as a surrogate endpoint for progression-free survival, potentially supporting faster review timelines. Should the PFS endpoint also meet statistical significance, iberdomide may qualify for priority review or conditional approval, strengthening its path to market in both the U.S. and EU.
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Business Significance
The EXCALIBER-RRMM results solidify BMS’s leadership in targeted protein degradation, a research platform the company has pioneered through its legacy immunomodulatory drugs (IMiDs®). Iberdomide could become a foundational therapy in combination regimens for relapsed or refractory multiple myeloma, a market projected to exceed $30 billion globally by 2030.
This innovation complements BMS’s existing hematology portfolio and provides a competitive edge against emerging therapies such as CAR-T cell treatments and bispecific antibodies. The company’s three-pronged approach to protein degradation—CELMoDs, ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs)—positions it as the only pharmaceutical firm to successfully commercialize multiple classes of protein degraders.
Patients’ Significance
Relapsed or refractory multiple myeloma remains a devastating disease, with most patients experiencing repeated relapses despite currently available therapies. The achievement of MRD negativity offers patients hope for deeper, longer-lasting remissions and the possibility of extending survival while maintaining quality of life. Iberdomide’s oral administration and manageable safety profile may also reduce the need for more intensive procedures like stem cell transplants or frequent infusions, improving convenience for patients and caregivers.
Policy Significance
The recognition of MRD as a regulatory endpoint reflects a broader shift toward precision medicine in oncology. As health authorities increasingly incorporate MRD-driven endpoints into approval frameworks, therapies like iberdomide could reach patients faster, aligning with global policy goals to expedite breakthrough cancer treatments. These results also support reimbursement discussions, as payers increasingly seek validated biomarkers to justify early access and premium pricing for innovative therapies.
Transaction Highlights
Bristol Myers Squibb continues to advance its proprietary CELMoD™ platform with iberdomide, a next-generation targeted protein degrader designed for multiple myeloma. The Phase 3 EXCALIBER-RRMM study demonstrated a statistically significant improvement in minimal residual disease (MRD) negativity rates when iberdomide was combined with standard therapies, compared to the control arm. The study enrolled approximately 664 patients, establishing 1.0 mg as the optimal dose. Iberdomide is being evaluated alongside daratumumab and dexamethasone (IberDd) versus the standard daratumumab, bortezomib, and dexamethasone (DVd) regimen. The trial will continue as planned to assess progression-free survival (PFS) and other secondary endpoints, including overall survival and safety. This achievement reinforces BMS’s strategic focus on targeted protein degradation and the CELMoD platform as a foundation for future combination therapies in hematology and oncology, offering the potential for meaningful new treatment options for relapsed or refractory multiple myeloma patients worldwide.
Source: Bristol Myers Squibb Press Release
