Key Takeaways:
The FDA granted accelerated approval to Bristol Myers Squibb's iberdomide (ZENBEXUS), the first CELMoD, for relapsed or refractory multiple myeloma as early as first relapse.
"Today's approval of ZENBEXUS represents meaningful progress for patients living with multiple myeloma and underscores the power of our targeted protein degradation platform," Cristian Massacesi, chief medical officer at Bristol Myers Squibb, said.
The decision rests on Phase 3 EXCALIBER-RRMM data showing ZDd achieved minimal residual disease (MRD)-negative complete response in 41% of patients (n=85) versus 21% (n=44) with daratumumab, bortezomib and dexamethasone (p<0.0001) at a median follow-up of 16 months. MRD-negativity, which detects one malignant cell among up to 1 million normal cells, is among the deepest measures of response and considered predictive of improved progression-free survival.
The approval marks the first in relapsed or refractory multiple myeloma based on MRD-negative complete response, a surrogate endpoint. Full approval is contingent on verification in confirmatory trials, with progression-free survival data from EXCALIBER-RRMM expected this year.
Iberdomide is an oral cereblon E3 ligase modulator that degrades the transcription factors Ikaros and Aiolos, producing direct antimyeloma and immune-stimulatory effects. The recommended dose is 1 mg orally once daily on days 1 through 21 of each 28-day cycle, given with subcutaneous daratumumab and hyaluronidase-fihj 1800 mg and dexamethasone.
The prescribing information carries boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolism, with the drug available only through the restricted ZENBEXUS REMS program. Neutropenia occurred in 90.2% of patients and infections in 78.9%, with 7.8% discontinuing ZDd due to adverse reactions. Serious adverse reactions affected 58.3% of patients, led by pneumonia (26%), while fatal adverse reactions occurred in 4.9%.
The approval was granted under the FDA's Project Orbis initiative and received Breakthrough Therapy designation. Bristol Myers Squibb is also advancing mezigdomide, an investigational CELMoD, with an FDA decision expected by May 13, 2027.
The approval strengthens Bristol Myers Squibb's position in the multiple myeloma market, where its immunomodulatory drugs helped establish the current standard of care. Investors will watch confirmatory progression-free survival data from EXCALIBER-RRMM, expected this year, which will determine whether the accelerated approval converts to full approval.
This article is for informational purposes only and does not constitute investment advice.
