Bristol-Myers Squibb Gains FDA Accelerated Approval for Iberdomide in Relapsed or Refractory Multiple Myeloma

A mandatory ZENBEXUS REMS program now governs every dispensing touchpoint for iberdomide (Zenbexus), after Bristol-Myers Squibb received FDA accelerated approval on August 13, 2026, for the agent in combination with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd) in adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.

The restricted distribution program is driven by a boxed warning covering embryo-fetal toxicity and serious venous and arterial thromboembolism. Specialty pharmacies and drug distributors handling Zenbexus must enroll in and operate under the REMS before any product release; failure to maintain compliant dispensing workflows carries direct regulatory exposure under 21 CFR Part 208. Additional prescribing information warnings address neutropenia, infections, and secondary primary malignancies, each requiring documented risk communication at the point of dispensing.

Efficacy data supporting the approval came from EXCALIBER-RRMM (NCT04975997), a two-stage, randomized, multicenter, open-label trial. The primary efficacy population comprised the first 420 patients randomized to iberdomide 1 mg with Dd (n=207) or the comparator daratumumab, bortezomib, and dexamethasone arm (DVd, n=213). The MRD-negative complete response rate at any time reached 41% (95% CI: 34, 48) in the IberDd arm versus 21% (95% CI: 15, 27) in the DVd arm (p<0.0001). Patients with disease refractory to prior anti-CD38 monoclonal antibody therapy or prior bortezomib were excluded from the trial population, a boundary that QA and regulatory teams should note when evaluating real-world use against label scope.

The review was conducted under Project Orbis, the FDA Oncology Center of Excellence initiative enabling concurrent multinational oncology submissions. Switzerland's Swissmedic participated in this review cycle, reinforcing Project Orbis as an active pathway for sponsors seeking parallel regulatory progress across ICH-aligned markets. For regulatory affairs leads tracking global dossier strategy, the Swissmedic collaboration signals a broadening of the Project Orbis partner network beyond its earlier core participants.

The recommended dosage is iberdomide 1 mg orally once daily on Days 1 through 21 of a 28-day cycle, continuing until disease progression or unacceptable toxicity. The application carried priority review, breakthrough therapy, and orphan drug designations; as an accelerated approval, a confirmatory trial demonstrating clinical benefit will be required to convert the indication to full approval.

The confirmatory trial outcome will determine whether the MRD-negative CR endpoint translates into the overall survival signal needed to sustain the label long-term.

Source: FDA Drugs@FDA / What's New: Drugs RSS Feed, August 13, 2026.