Drug Update · Neurology

FDA Approves ofatumumab for Relapsing MS: Cuts Relapse Rate 51%

July 20, 2026

Study 1 ARR

0.11 vs 0.22 (51% relative reduction; p < 0.001)

Study 2 ARR

0.10 vs 0.25 (58% relative reduction; p < 0.001)

3-month confirmed disability progression (pooled)

10.9% vs 15.0% (relative risk reduction 34.3%; p = 0.003)

Approved dosing

20 mg SC at Weeks 0, 1, 2, then 20 mg monthly starting Week 4

Clinical Perspective

Neurologists and other clinicians treating adults with relapsing forms of MS now have an FDA-approved subcutaneous CD20-directed monoclonal antibody, ofatumumab (KESIMPTA), with trial evidence showing reductions in annualized relapse rate and in 3-month confirmed disability progression versus teriflunomide ^[2]. The approval and supporting data provide source-confirmed evidence to consider ofatumumab among high-efficacy DMTs, alongside other monoclonal antibodies such as natalizumab that ranked highly for disability outcomes in a 2023 network meta-analysis ^[2]^[1]. Key prescribing considerations from the label include pre-treatment HBV screening, baseline quantitative immunoglobulins and liver tests, and vaccination timing given recommendations about live vaccines ^[2].

Dr. Vikram Patel · Neurology

The FDA approved ofatumumab (KESIMPTA) for the treatment of relapsing forms of multiple sclerosis in adults based on two randomized, double-blind, active-comparator trials that showed reductions in annualized relapse rate versus teriflunomide 14 mg and a pooled reduction in 3-month confirmed disability progression ^[2]. Clinicians should consult current prescribing information for full dosing guidance. In Study 1, KESIMPTA lowered the annualized relapse rate to 0.11 versus 0.22 with teriflunomide (51% relative reduction; p < 0.001) and in Study 2 to 0.10 versus 0.25 (58% relative reduction; p < 0.001) ^[2].

Clinical Context

Ofatumumab (KESIMPTA) is a CD20-directed cytolytic monoclonal antibody manufactured and marketed under the KESIMPTA label and is indicated for relapsing forms of MS in adults ^[2]. The mechanism described in the prescribing information is binding to CD20 on B lymphocytes with subsequent antibody-dependent cellular cytolysis and complement-mediated lysis ^[2]. Comparative efficacy assessments from a 2023 network meta-analysis identified monoclonal antibody therapies among the most efficacious disease-modifying therapies for relapsing MS; ofatumumab and other anti-CD20/monoclonal antibody agents ranked highly across relapse and disability outcomes, and natalizumab was among the top treatments for 6-month confirmed disability progression in that analysis ^[1]. The FDA prescribing information and the network meta-analysis together position ofatumumab among high-efficacy DMT options for clinicians treating adults with relapsing MS ^[2]^[1].

Key Findings

The two pivotal randomized, double-blind, double-dummy, active comparator trials reported in the KESIMPTA prescribing information showed KESIMPTA reduced the annualized relapse rate (ARR) to 0.11 versus 0.22 with teriflunomide in Study 1 (51% relative reduction; p < 0.001) and to 0.10 versus 0.25 in Study 2 (58% relative reduction; p < 0.001) ^[2].
A prospective pooled analysis of Studies 1 and 2 showed a reduction in the proportion of patients with 3-month confirmed disability progression: 10.9% on KESIMPTA versus 15.0% on teriflunomide, a relative risk reduction of 34.3% (p = 0.003) ^[2].
MRI outcomes favored KESIMPTA: mean number of T1 gadolinium-enhancing lesions per scan was 0.01 versus 0.46 in Study 1 and 0.03 versus 0.52 in Study 2 (relative reductions 98% and 94%, respectively), and the number of new or enlarging T2 lesions per year was 0.72 versus 4.00 in Study 1 and 0.64 versus 4.16 in Study 2 (relative reductions 82% and 85%, respectively) ^[2].
A network meta-analysis of DMTs for relapsing MS ranked monoclonal antibody therapies, including ofatumumab among the most efficacious therapies across ARR and confirmed disability progression outcomes, with natalizumab appearing among the top three for 6-month confirmed disability progression in that analysis ^[1].

Safety & Tolerability

Prior to initiating KESIMPTA, patients should be screened for Hepatitis B virus (HBV) because KESIMPTA is contraindicated in patients with active HBV confirmed by positive Hepatitis B surface antigen (HBsAg) and anti-HBV tests ^[2].
Quantitative serum immunoglobulins should be obtained prior to initiating KESIMPTA; for patients with low serum immunoglobulins, consultation with immunology experts is advised before starting treatment ^[2].
Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer immunizations according to immunization guidelines at least 4 weeks prior to initiation for live or live-attenuated vaccines and, when possible, at least 2 weeks prior to initiation for inactivated vaccines ^[2].
Prior to initiating KESIMPTA, obtain baseline liver function tests including ALT, AST, alkaline phosphatase, and bilirubin ^[2].
The first injection of KESIMPTA should be performed under the guidance of a healthcare professional ^[2].

Study Design

The approval is based on two randomized, double-blind, double-dummy, active comparator-controlled clinical trials (Study 1, N=927 randomized; Study 2, N=955 randomized) that compared KESIMPTA 20 mg subcutaneously to teriflunomide 14 mg orally once daily ^[2]. Clinicians should consult current prescribing information for full dosing guidance. The primary endpoint in both trials was annualized relapse rate over the treatment period; additional outcomes included time to 3-month confirmed disability progression, number of T1 gadolinium-enhancing lesions per scan, and annualized rate of new or enlarging T2 lesions ^[2]. Trial results and pooled analyses are reported in the KESIMPTA prescribing information ^[2].

FAQ

Q1 What is ofatumumab (KESIMPTA) approved for?

KESIMPTA (ofatumumab) is approved for the treatment of relapsing forms of multiple sclerosis in adults, including clinically isolated syndrome, relapsing‑remitting disease, and active secondary progressive disease, as stated in the prescribing information. The approval is supported by two randomized, double‑blind, active‑comparator trials comparing KESIMPTA with teriflunomide.

Q2 How does ofatumumab (KESIMPTA) work?

Ofatumumab is a CD20‑directed cytolytic monoclonal antibody that binds to CD20 on pre‑B and mature B lymphocytes; following cell‑surface binding, it results in antibody‑dependent cellular cytolysis and complement‑mediated lysis of B lymphocytes, a mechanism described in the prescribing information.

Q3 What is the recommended dose of ofatumumab (KESIMPTA)?

The recommended dosing in the prescribing information is 20 mg administered by subcutaneous injection at Weeks 0, 1, and 2 (initial dosing), followed by 20 mg administered once monthly starting at Week 4. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of ofatumumab (KESIMPTA)?

[Information] was not available in the provided source excerpts.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves ofatumumab for Relapsing MS: Cuts Relapse Rate 51%

FDA Approves ofatumumab for Relapsing MS: Cuts Relapse Rate 51%

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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