The Food and Drug Administration has granted accelerated approval to ZENBEXUS (iberdomide), the first drug in a new class for multiple myeloma, giving patients a fresh option as early as their first relapse. Bristol Myers Squibb announced the August 13 clearance for ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone, a regimen abbreviated ZDd [1].
ZENBEXUS is the first CELMoD therapy, a cereblon-modulating agent designed to tag cancer-driving proteins for destruction [1]. The FDA cleared it for adults with multiple myeloma who have received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent, which places it as early as first relapse [1].
The approval rests on the Phase 3 EXCALIBER-RRMM trial. Among 207 patients on the ZDd regimen, 41% (n=85) reached a minimal-residual-disease-negative complete response, meaning no cancer detectable by a sensitive test, compared with 21% (n=44) of the 213 patients on the comparator regimen of daratumumab, hyaluronidase, and dexamethasone; the difference was statistically significant, at a median follow-up of 16 months [1].
"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, the trial's lead investigator [1]. Cristian Massacesi, the company's chief medical officer, said the clearance "represents meaningful progress for patients living with multiple myeloma" [1].
The caution is written into the approval. This is an accelerated approval, granted on a surrogate endpoint, the MRD-negative complete response, rather than on proof that patients live longer. A deeper remission measured in the lab is a strong signal, not the same thing as more years of life, and Bristol Myers Squibb states that full approval for this indication will be contingent on verification of clinical benefit in a confirmatory trial [1]. Multiple myeloma remains incurable, and that longer-term evidence is still pending.
