How effective is Kasimpta (ofatumumab) in preventing multiple sclerosis (MS) disability in patients with a single lesion?

Kasimpta Efficacy in Single-Lesion MS

The evidence does not specifically address Kasimpta's efficacy in patients with just one lesion, as clinical trials enrolled patients with more active disease requiring at least one relapse plus MRI activity or multiple lesions. However, based on the pivotal trial data and mechanism of action, Kasimpta demonstrates robust disability prevention in relapsing MS through near-complete B-cell depletion.

Clinical Trial Evidence for Disability Prevention

Kasimpta significantly reduced the risk of 3-month confirmed disability progression compared to teriflunomide in two identical phase 3 trials (ASCLEPIOS I/II). 1

Key Efficacy Outcomes:

• Annualized relapse rate reduction: Kasimpta significantly lowered ARR compared to teriflunomide in both pivotal studies 1
• Disability progression: Kasimpta significantly reduced the risk of 3-month confirmed disability progression versus active comparator 1
• MRI activity suppression: >99% suppression of new brain MRI lesion activity across all doses studied, with statistically significant reductions (p < 0.001) in new T1 gadolinium-enhancing lesions and new/enlarging T2 lesions 2
• Neuronal injury marker: Superior efficacy on serum neurofilament light chain levels, indicating reduced neuronal damage 3

Important Context: Trial Enrollment Criteria

The pivotal trials specifically enrolled patients with more active disease than a single lesion scenario 1:

• Required at least one relapse in the previous year PLUS
• Two relapses in the previous 2 years, OR
• Presence of a T1 gadolinium-enhancing lesion in the previous year
• Mean number of T1 GdE lesions at baseline was 1.5-1.6 1

This means patients with only one lesion and no clinical relapses would not have met enrollment criteria for the studies that established Kasimpta's efficacy. 1

Mechanism Supporting Efficacy

• Rapid and sustained B-cell depletion: Near-complete depletion achieved through stepwise dosing (Weeks 0,1,2) followed by monthly 20 mg maintenance, largely independent of body weight or other factors 3
• High potency and affinity: Fully human anti-CD20 monoclonal antibody with unique binding site and higher affinity to B cells compared to previous anti-CD20 therapies 3
• Sustained effect: Long-term treatment up to 4 years shows continued tolerability with no new safety risks 3

Clinical Application Caveat

For a patient with truly just one lesion and no clinical relapses, the decision to initiate any high-efficacy therapy like Kasimpta requires careful consideration, as this represents less active disease than studied populations. The 2025 ECTRIMS/EBMT guidelines show that ongoing trials comparing high-efficacy therapies (including ofatumumab) require "one or more clinical relapse OR MRI activity" as minimum disease activity criteria. 4

Real-World Usage Pattern:

• In real-world practice post-FDA approval, 58.4% of patients starting Kasimpta were DMT-naïve at 9 months, suggesting expanding use in less heavily pre-treated populations 5
• Most patients (81.7%) did not experience relapse during the pre-index period, indicating use in patients with lower recent activity 5
• Majority had mild MS disability levels (64.7%) 5

Network Meta-Analysis Comparison

Kasimpta demonstrates efficacy comparable to other highly efficacious monoclonal antibody DMTs (alemtuzumab, natalizumab, ocrelizumab) for reducing relapse and disability progression risk in relapsing MS. 6