Novartis Pharma AG

Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0033 - Baseline serum neurofilament light levels have prognostic value for on-study MRI activity: Results from ASCLEPIOS trials (ID 1669)

Speakers
Presentation Number
P0033
Presentation Topic
Biomarkers and Bioinformatics

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.

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Clinical Trials Poster Presentation

P0209 - Efficacy and safety of ofatumumab versus placebo in relapsing multiple sclerosis patients in Japan and Russia: Results from the Phase 2 APOLITOS study (ID 1656)

Speakers
Presentation Number
P0209
Presentation Topic
Clinical Trials

Abstract

Background

Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide with a favorable safety profile in the Phase 3 ASCLEPIOS I/II trials in relapsing multiple sclerosis (RMS) patients (Global, Ex-Japan). APOLITOS was designed to support ofatumumab registration for RMS treatment in Japan in conjunction with ASCLEPIOS.

Objectives

To evaluate the efficacy and safety of ofatumumab versus placebo in RMS patients and assess consistency of effect in Japanese and non-Japanese patients.

Methods

APOLITOS was a 24-week, double-blind, placebo-controlled study followed by an open-label extension up to week 48. Patients aged 18–55 years with confirmed MS diagnosis (2010 revised McDonald criteria), prior evidence of disease activity (≥1 relapse in the last 2 years AND MRI activity in the last year), and an EDSS score of 0–5.5 were randomized (2:1) to subcutaneous ofatumumab 20 mg or matching placebo (initial doses: Days 1, 7, 14, week 4; subsequent doses: every 4 weeks). Randomization was stratified by region (Japan or ex-Japan) and baseline gadolinium-enhancing (Gd+) T1 lesions (0 or ≥1). The primary endpoint was a reduction in cumulative number of Gd+ T1 lesions across weeks 12, 16, 20, and 24. Secondary outcomes included consistency in reduction of Gd+ T1 lesions across regions, annualized relapse rate (ARR), and safety.

Results

In total, 64 patients were randomized (32 each from Japan and Russia; by treatment: ofatumumab, N=43; placebo, N=21), and 59 completed the double-blind phase. The majority of patients had high baseline disease activity ([mean] 1.5 relapses in the last year, 1.2 Gd+ T1 lesions) and 69% received prior disease-modifying therapies. At week 24, ofatumumab significantly reduced Gd+ T1 lesions versus placebo by 93.6% (p<0.001); the results were consistently in favor of ofatumumab across regions. Ofatumumab reduced the ARR versus placebo by 58.0% (p=0.119). Adverse events occurred in 69.8% of patients with ofatumumab and 81.0% with placebo; injection-related reactions were the most common (20.9% and 19.0%, respectively). One ofatumumab-treated patient was diagnosed with serious chronic inflammatory demyelinating polyradiculoneuropathy after completing the study. No deaths, opportunistic infections, or malignancies occurred during the study.

Conclusions

Ofatumumab demonstrated superior efficacy versus placebo in a RMS population with recent disease activity in Japanese and non-Japanese patients. No new safety signals were observed and the results were consistent with the Phase 3 ASCLEPIOS I/II trials.

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