Author Of 2 Presentations
P0033 - Baseline serum neurofilament light levels have prognostic value for on-study MRI activity: Results from ASCLEPIOS trials (ID 1669)
Abstract
Background
In the ASCLEPIOS I/II trials, ofatumumab significantly lowered serum neurofilament light (sNfL) levels, a marker of disease activity and treatment response, in the first assessment at month 3 and at all subsequent visits versus teriflunomide.
Objectives
To investigate the prognostic value of baseline sNfL for on-study disease activity and worsening in patients with relapsing MS, particularly in newly diagnosed, treatment-naïve patients.
Methods
Patients (pooled N=1882) were randomized to ofatumumab or teriflunomide, receiving treatment for up to 30 months. Patients were stratified by median baseline sNfL levels. We assessed annual on-study T2 lesion formation and brain volume loss (BVL, Jacobian integration) by sNfL category in all patients and in the subgroup of newly diagnosed within 3 year of screening without prior disease-modifying treatment (representing natural course of sNfL and disease at baseline) at month 24 or end of study. The annualized rate of new or enlarging T2 (neT2) lesions in year-2 versus year-1 was assessed in all patients by sNfL category (negative binomial model with time [in year] as offset).
Results
Patients with high sNfL (>median) levels at baseline developed more neT2 lesions per year on study than patients with low (≤median) sNfL levels (adjusted mean rate: ofatumumab: 0.95 vs 0.39, relative increase 143%, p<0.001; teriflunomide 5.28 vs 3.02, relative increase 74.5%, p<0.001). The prognostic value of baseline sNfL persists for year-2 (high vs low, ofatumumab: 0.09 vs 0.06, 64.5%, p=0.124; teriflunomide 4.53 vs 3.12, 45.6%, p=0.003. A single sNfL assessment at baseline had no prognostic value for on-study relapses and disability worsening. Patients with high baseline sNfL had higher annualized rate of BVL than patients with low sNfL (ofatumumab: 0.32% vs 0.23%, relative difference 37.3%, p=0.045; teriflunomide: 0.43% vs 0.29%, relative difference 49.4%, p<0.001). The results were consistent in the subgroup of newly diagnosed, treatment-naïve patients. The relative treatment effect of ofatumumab versus teriflunomide was similar across all measures in both the high and low sNfL groups.
Conclusions
Baseline sNfL levels were prognostic for on-study lesion formation and BVL for at least 2 years, in all patients and in the subgroup of newly diagnosed, treatment-naïve patients. sNfL levels can supplement clinical assessments and help identify patients at high risk for future disease activity.
P0192 - Benefit-risk of ofatumumab in treatment-naïve early relapsing multiple sclerosis patients (ID 1601)
Abstract
Background
Ofatumumab, a fully human anti-CD20 monoclonal antibody with a monthly 20 mg s.c. dosing regimen, demonstrated superior efficacy vs teriflunomide and a favorable safety profile in the Phase 3 ASCLEPIOS I/II relapsing multiple sclerosis (RMS) trials.
Objectives
To evaluate the benefit-risk profile of ofatumumab treatment in patients with early RMS in the Phase 3 ASCLEPIOS I/II trials.
Methods
Key efficacy and safety outcomes were assessed in the subgroup of 615 newly diagnosed (within 3 years before screening), treatment-naïve (no prior disease-modifying therapy [DMT] use) patients who received ofatumumab or teriflunomide as a first-line therapy in ASCLEPIOS I/II trials (32.7% of the total 1882 patients).
Results
Baseline characteristics of the newly diagnosed, treatment-naïve subgroup were typical of early MS patients (median age and MS duration since diagnosis (years) were 36 and 0.35, respectively). Compared to patients on teriflunomide, ofatumumab reduced ARR by 50.3% (0.09 vs 0.18; p<0.001), 3mCDW risk by 38% (10.1% vs 12.8%; p=0.065), 6mCDW risk by 46% (5.9% vs 10.4%; p=0.044), gadolinium-enhancing T1 lesions/scan by 95.4% (0.02 vs 0.39: p<0.001), and new/enlarging T2 lesions/year by 82.0% (0.86 vs 4.78, p<0.001). Treatment-emergent adverse events (AEs) occurred in 84.7% ofatumumab vs 86.0% teriflunomide-treated patients; serious AEs were reported in 7.0% and 5.3%, respectively. No cases of malignancies were reported in this newly diagnosed subgroup, randomized to either drug. Infection rates were comparable between ofatumumab (56.1%) and teriflunomide (56.5%); serious infections rates were 1.9% and 0.7%, respectively, and no opportunistic infections were reported. Systemic injection reactions were only imbalanced between ofatumumab and teriflunomide (with placebo injections) at the first injection given at the study site, and 99.8% of injection reactions were mild-to-moderate in this subgroup; after the 4th injection, >70% RMS patients self-injected at home. Compliance of all patients with ofatumumab was high (98.8%).
Conclusions
Ofatumumab is the first high efficacy DMT that can be self-administered at home, as demonstrated in Phase 3 ASCLEPIOS I/II trials. Ofatumumab showed superior efficacy vs teriflunomide in newly diagnosed, treatment-naïve patients with low absolute relapse rates, very low MRI lesion activity and prolonged time to disability worsening, consistent with the overall study population.