Daratumumab Shows Promise in NMOSD as FDA Accepts Iberdomide NDA for Multiple Myeloma
Phase 3 trial data show daratumumab reduced relapse risk by 74% in NMOSD. Separately, the FDA accepted an NDA for iberdomide plus daratumumab/dexamethasone in relapsed/refractory multiple myeloma, with a PDUFA date of August 17, 2026.
Treatment with daratumumab, a monoclonal antibody approved for multiple myeloma, was associated with a significant decrease in relapse risk in patients with aquaporin-4 immunoglobulin G (AQP4-IgG) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) compared with placebo, according to data from a randomized, double-blind, phase 3 trial. Separately, the FDA has accepted a new drug application (NDA) seeking approval for iberdomide plus daratumumab and dexamethasone as a treatment for patients with relapsed/refractory multiple myeloma.
Daratumumab in NMOSD
The DAWN trial enrolled 135 patients between November 2022 and March 2025. Patients were randomized 2:1 to daratumumab (84% women; mean age, 51.3 years) or placebo (87% women; mean age, 54.3 years). Daratumumab was dosed at 8 mg/kg intravenous every 2 weeks during an induction phase, then 4 mg/kg intravenous every 4 weeks during maintenance, for at least 52 weeks. All patients received background low-dose prednisone (7.5 mg).
In the per protocol analysis, significantly more patients in the daratumumab group were relapse free at 156 weeks than those in the placebo group (69.1% vs 14.6%). The overall decrease in relapse risk in the treatment group was 74% (hazard ratio [HR], 0.26; P < .001). The overall HR in the intention-to-treat population was 0.255 (P < .001). Similar results were reported on subgroup analysis by sex, age, disease duration, baseline EDSS score, and concomitant autoimmune disorders.
In patients who relapsed, transverse myelitis (53% daratumumab, 74% placebo) and optic neuritis (24% vs 26%) were most common. Just 6% of those in the daratumumab group experienced EDSS worsening vs 36% of those in the placebo group. Adverse event rates were similar between daratumumab and placebo (88% vs 84%, respectively), and treatment-related AEs occurred in 28% vs 22%.
Daratumumab targets CD38, a protein that is highly expressed on plasma cells and plasmablasts, which produce AQP4 antibodies that damage astrocytes. No existing therapies for NMOSD target CD38.
The findings were presented on February 7 at Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026.
Iberdomide NDA for Relapsed/Refractory Multiple Myeloma
The FDA has accepted an NDA seeking approval for iberdomide plus daratumumab and dexamethasone as a treatment for patients with relapsed/refractory multiple myeloma, according to a press release from Bristol Myers Squibb. The agency has assigned a Prescription Drug User Fee Act date of August 17, 2026, for approving the iberdomide regimen. The FDA also conferred breakthrough therapy designation and priority review for this indication.
Supporting data for the NDA came from the phase 3 EXCALIBER-RRMM trial (NCT04975997) evaluating iberdomide plus daratumumab/dexamethasone vs daratumumab plus bortezomib and dexamethasone (DVd) among those with relapsed/refractory multiple myeloma. The filing was supported by findings from a planned analysis of minimal residual disease (MRD) negativity rates. In September 2025, developers announced that the iberdomide-based regimen yielded a statistically significant MRD negativity rate improvement vs the control arm. Based on a recommendation from a data monitoring committee, the study was to continue without any modifications to assess patients for end points including progression-free survival, overall survival, and safety. At the time of the analysis, the safety profile of the iberdomide regimen was comparable with previous reports of each agent.
As part of the 2-stage, multicenter, open-label EXCALIBER-RRMM trial, patients were randomly assigned to receive daratumumab plus iberdomide and dexamethasone across 3 dosing levels or DVd. Patients in the experimental arm received iberdomide at 1.0, 1.3, or 1.6 mg on days 1 to 21 of each 28-day cycle. The trial's primary end points were PFS and MRD-negative complete responses at any time. Secondary end points included OS, sustainability of MRD negativity, ORR, time to response, duration of response, time to progression, time to next treatment, PFS2, safety, and quality of life.
Patients 18 years and older with multiple myeloma and measurable disease, 1 to 2 prior lines of treatment, and documented disease progression during or after the most recent line of treatment were eligible for enrollment. Having an ECOG performance status of 0 to 2 was another requirement for study entry.