The U.S. Food and Drug Administration has granted accelerated approval to Bristol Myers Squibb's Zenbexus (iberdomide), in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDh), for adults with multiple myeloma who have received at least one prior line of treatment that included a proteasome inhibitor and immunomodulatory agent.
Multiple myeloma is an incurable but treatable blood cancer that originates in bone marrow plasma cells. It causes abnormal cells to multiply uncontrollably, crowding out healthy blood cells and releasing proteins that damage bones and kidneys.
The American Cancer Society estimates that in 2026 about 36,000 Americans will be newly diagnosed with the disease, which has a five-year survival rate of 62.4%.
The FDA's accelerated approval pathway allows promising drugs for serious diseases to reach patients sooner based on an early measure that is expected to predict clinical benefit. Drugmakers must then conduct additional studies to confirm that benefit.
Zenbexus is the first FDA-approved cereblon E3 ligase modulating drug, or CELMoD, for multiple myeloma, Bristol Myers Squibb said in a statement. The FDA’s accelerated approval is based on results from the Phase 3 EXCALIBER-RRMM trial.
In the trial, 41% of patients treated with the Zenbexus combination achieved a minimal residual disease-negative complete response, compared with 21% of patients who received daratumumab, bortezomib and dexamethasone. The difference was statistically significant.
Minimal residual disease refers to the small number of cancer cells that may remain in the body after treatment and cannot be detected using conventional diagnostic methods. MRD negativity does not necessarily mean all cancer cells are gone, but it is considered predictive of improved progression-free survival.
“The FDA approval of iberdomide marks the anticipated arrival of a new therapeutic class for relapsed or refractory multiple myeloma and has the potential to make a meaningful difference for patients,” said Sagar Lonial, M.D., FACP, FASCO, EXCALIBER-RRMM lead investigator and chief medical officer of the Winship Cancer Institute of Emory University.
Bristol Myers Squibb Chief Medical Officer Cristian Massacesi said the approval represents progress for patients with multiple myeloma and for the company's targeted protein degradation platform.
“Today’s approval of Zenbexus represents meaningful progress for patients living with multiple myeloma and underscores the power of our targeted protein degradation platform, particularly our CELMoD programs,” Massacesi said on Thursday.
“As the first approved CELMoD, Zenbexus marks the arrival of a new treatment class and is an important milestone in our efforts to expand what is possible for patients with multiple myeloma,” Massacesi said.
The Zenbexus combination had a safety profile that is expected of the combination, according to the company. About 7.8% of patients discontinued Zenbexus because of adverse reactions.
The FDA review was conducted under the FDA's Project Orbis initiative, which allows concurrent review by health authorities in several countries.
The EXCALIBER-RRMM trial continues to evaluate progression-free survival, one of its two primary endpoints. Bristol Myers Squibb said full trial data are expected later this year.
Bristol Myers Squibb, based in Princeton, also has a new drug application under FDA review for mezigdomide, an investigational CELMoD, in combination with carfilzomib and dexamethasone. The FDA's target date for a decision is May 13, 2027.
