Ofatumumab (Arzerra) in clinical studies for Multiple Sclerosis (MS)

Ofatumumab is an antibody against a protein called CD20, which is found on the surface of certain types of immune cells called B-cells. It is marketed and developed by the Danish biotech company Genmab under a co-development and commercialization agreement with Novartis.

Ofatumumab was originally developed under an agreement with GlaxoSmithKline (GSK). In August 2015, Novartis purchased all remaining rights to ofatumumab from GSK.

Under the brand name Arzerra, the drug is approved by the U.S. Food and Drug Administration (FDA) to treat chronic lymphocytic leukemia — and clinical trials are ongoing into its potential to treat other diseases, such as follicular lymphoma and relapsing multiple sclerosis (RMS).

Preclinical studies in animal models provided promising results, which helped developers proceed to Phase 1 clinical trials in healthy volunteers. With positive safety and toxicity findings from these trials, the companies moved forward to Phase 2 clinical trials, which started in November 2011 and are now complete.

A pilot Phase 2 trial (NCT00640328) with a small cohort of 38 RMS patients was carried out in 2011, with different doses of ofatumumab for 48 weeks. A considerable reduction in the formation of brain plaques was seen, along with a reduction in the number of autoimmune B-cells. New plaque formation also appeared to be suppressed. These results were published in the scientific journal, Neurology.

These findings paved the way for a second, larger Phase 2 trial, called MIRROR (NCT01457924), with 232 RMS taking part in the multicenter, double-blind, placebo-controlled study. Participants were randomized to one of five treatment groups: placebo, ofatumumab 3 mg every 12 weeks, ofatumumab 30 mg every 12 weeks, ofatumumab 60 mg every 12 weeks, or ofatumumab 60 mg every four weeks. All continued in the study for 24 weeks of treatment and until B-cell depletion (or destruction). Results showed that ofatumumab was able to “deplete B cells quickly” depending on the dose used and frequency of administration, and effectively reduced the formation of new brain plaques relative to placebo. No new or unexpected safety findings were recorded.

Two randomized and double-blind Phase 3 studies, ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231), are currently recruiting relapsing MS patients across the U.S., and in Canada and Europe. These studies will compare the efficacy and safety of ofatumumab, injected under the skin (subcutaneous), versus teriflunomide (Aubagio), an approved MS-treatment, in about 900 people. Participants will receive either ofatumumab every four weeks or teriflunomide once daily. The trial’s primary goal is annualized MS relapse rates, or the number of confirmed relapses in 12 months, recorded over 2.5 years. Secondary goals include measures of disease progression from baseline according to Expanded Disability Status Scale (EDSS) scores.