BMS CELMoD Mezigdomide Doubles PFS in Myeloma as FDA Reviews Iberdomide

Bristol Myers Squibb presented data at the American Society of Clinical Oncology annual meeting demonstrating that its CELMoD candidate mezigdomide more than doubled progression-free survival in patients with relapsed or refractory multiple myeloma, while the FDA has started a priority review of another BMS CELMoD, iberdomide, with a decision expected by August 17.

The data come from 479 patients analyzed in the phase 3 SUCCESSOR-2 trial testing mezigdomide in combination with Amgen's Kyprolis and dexamethasone versus that pair alone. Patients in the mezigdomide arm lived without disease progression for an average of 18 months, compared to 8.3 months for those given just Kyprolis and dexamethasone. The mezigdomide regimen cut the risk of disease progression or death by 52%. Mezigdomide also nearly tripled the complete response rate to 26.7% compared to 8.9% in the control arm, despite patients in the study being heavily pretreated.

Overall survival data are immature, but the curves are already beginning to separate. Side effects were worse in the mezigdomide arm, with 83.7% of patients reporting grade 3 or 4 adverse events related to treatment versus 56.5% in the control cohort. The safety profile is consistent with prior trials, and side effects were described as manageable.

BMS plans to discuss the mezigdomide data with the FDA at a future point. Meanwhile, the FDA has started a priority review of iberdomide as an add-on to Johnson & Johnson and Genmab's Darzalex (daratumumab) and dexamethasone for relapsed or refractory multiple myeloma. The filing is based on the EXCALIBER-RRMM study, which found a statistically significant improvement in minimal residual disease negativity compared to the control arm. The trial is continuing to assess progression-free survival and overall survival. Iberdomide has been awarded breakthrough status by the FDA.

CELMoD drugs — cereblon E3 ligase modulators — have not yet had an FDA approval. They are similar to BMS's approved protein degraders thalidomide, Revlimid and Pomalyst, and are designed to target transcription factors called Ikaros and Aiolos, which multiple myeloma relies on. BMS's blood cancer franchise is already facing generic competition to Revlimid and Pomalyst, sales of which were halved last year to $2.35 billion and fell 23% to $2.34 billion, respectively. Analyst forecasts for iberdomide's peak sales range from just over $1 billion to $5 billion.

All three of BMS's CELMoDs — iberdomide, mezigdomide, and golcadomide (for lymphoma) — were acquired as part of the group's $74 billion merger with Celgene in 2019. Mezigdomide was highlighted in IQVIA's new drugs to watch in 2026 report, which said that if two phase 3 trials (SUCCESSOR-1 and SUCCESSOR-2) are positive, sales could reach nearly $1.5 billion in 2031.

A potential rival in the CELMoD category is C4 Therapeutics, whose cemsidomide has dosed the first patient in its Phase 2 MOMENTUM trial evaluating cemsidomide combined with dexamethasone for relapsed/refractory multiple myeloma. The open-label, single-arm study will enroll approximately 100 patients who have received at least three prior anti-myeloma regimens. Enrollment is expected to complete in the first quarter of 2027. C4 Therapeutics also plans to initiate a Phase 1b trial combining cemsidomide with elranatamab in the second quarter of this year. Other CELMoD candidates are in early-stage development at Nurix (zelebrudomide) and Gluetacs (GT919 and GT929).