The US FDA has accepted for review a New Drug Application submitted by Bristol Myers Squibb (NYSE: BMY) for molecular glue drug mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) in patients with relapsed or refractory multiple myeloma, assigning a PDUFA target action date of May 13, 2027. The filing targets patients with relapsed or refractory multiple myeloma who are triple-class exposed and refractory to both lenalidomide and anti-CD38 antibodies, a population with limited treatment options and poor outcomes.
The NDA is supported by results from the Phase III SUCCESSOR-2 trial (NCT05552976), which demonstrated a statistically significant improvement in progression-free survival with MeziKd versus carfilzomib and dexamethasone alone — 18.0 months versus 8.3 months, respectively, with a hazard ratio of 0.48. Results were presented as a late-breaking oral presentation at the 2026 American Society of Clinical Oncology Annual Meeting and published in The Lancet. The trial enrolled 479 patients, of whom 92.1% were triple-class exposed, 85.8% were refractory to an anti-CD38 monoclonal antibody, and 75.8% were refractory to lenalidomide, making it one of the most heavily pretreated populations examined in a randomized multiple myeloma trial of this scale.
Mezigdomide is an oral cereblon E3 ligase modulator (CELMoD) designed to induce degradation of the transcription factors Ikaros and Aiolos, promoting myeloma cell death while enhancing T cell activity. Compared with earlier immunomodulatory drugs such as lenalidomide and pomalidomide, it is intended to retain activity in tumors that have become refractory to conventional IMiD therapy.
Current treatment for lenalidomide- and anti-CD38-refractory patients largely consists of pomalidomide-based triplets, such as daratumumab plus pomalidomide and dexamethasone, or carfilzomib doublets, neither of which produces durable responses in this population. BCMA-directed therapies including belantamab mafodotin (Blenrep), teclistamab (Tecvayli), and linvoseltamab (Lynozyfic) address later-line disease but carry significant toxicity burdens and, in the case of CAR-T cell therapies such as ciltacabtagene autoleucel and idecabtagene vicleucel, substantial logistical barriers. MeziKd, if approved, would offer an oral, non-BCMA option with a PFS benefit that meaningfully exceeds what the control arm of SUCCESSOR-2 produced, in a population where such improvement has been difficult to achieve.
Bristol Myers Squibb has described mezigdomide as part of a targeted protein degradation platform built over more than two decades. The company pioneered the cereblon-targeting IMiD class, whose protein degradation mechanism was elucidated after the drugs entered clinical use, and now views CELMoDs as the next generation of that platform. Alongside the MeziKd combination, BMS is also evaluating mezigdomide (an experimental CELMoD) combined with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) in the ongoing Phase III SUCCESSOR-1 trial.