Other names: GSK 1841157, Kesimpta
Ofatumumab for relapsing remitting MS: Appraisal
Ofatumumab is an experimental drug treatment for relapsing remitting MS. In clinical trials it has been taken as an injection under the skin (subcutaneous).
- Ofatumumab reduces the number of B cell lymphocytes, a type of white blood cell which is thought to influence the abnormal immune response that causes the attack on the myelin coating of nerves.
- In relapsing remitting MS, ofatumumab reduced relapse rates by 50-59% compared to Aubagio.
- In phase III studies, the most frequent side effects were injection-related reactions. Other side effects included blocked nose, headache, and chest and bladder infections.
Licensing and appraisal
The MHRA (Medicines and Healthcare products Regulatory Agency) has granted marketing authorisation for ofatumumab to treat relapsing remitting multiple sclerosis where people are having relapses or showing new lesions on MRI scans.
NICE has begun an appraisal of ofatumumab for relapsing remitting MS to decide whether it should be prescribed by the NHS in England and Wales. The MS Trust is taking part in this appraisal. A decision is expected to be published before the end of April.
The Scottish Medicines Consortium (SMC) has also begun their appraisal to decide whether ofatumumab can be prescribed by the NHS in Scotland. The MS Trust is contributing to the appraisal. A decision is expected later this year.
Northern Ireland will carry out a separate appraisal.
How does ofatumumab work?
Ofatumumab is a monoclonal antibody, a type of drug developed to attack specific targets in the immune system. Ofatumumab has been designed to bind to a marker (CD20) on the surface of B cell lymphocytes, a type of white blood cell which is thought to influence the abnormal immune response that causes the attack on the myelin coating of nerves. Targeted B cells are destroyed.
Ofatumumab is currently used as a treatment for chronic lymphocytic leukaemia.
How is ofatumumab taken?
Ofatumumab is taken as an injection under the skin.
What are the results so far?
An initial phase II trial evaluated ofatumumab given as an intravenous infusion; the drug is now being developed as a subcutaneous injection.
In a phase II clinical trial, 38 participants received 2 ofatumumab infusions (100 mg, 300 mg, or 700 mg) or placebo 2 weeks apart. After 24 weeks, the participants first treated with placebo were treated with ofatumumab and patients who were initially treated with ofatumumab received placebo. All patients were then followed for an additional 24 weeks.
Ofatumumab treatment produced a major reduction in B cell numbers. For all doses of ofatumumab, there was almost complete suppression of new active lesions seen on MRI.
- MIRROR - ofatumumab compared to placebo
232 participants took different doses of ofatumumab (3 mg, 30 mg, or 60 mg given every 12 weeks; 60 mg every 4 weeks, or placebo) for a 24-week treatment period. The main measure of the study was the number of new active MRI lesions at week 12. All doses resulted in 65% reduction in new active MRI lesions. Based on data collected from weeks 4 to 12, those taking cumulative doses of at least 30mg showed more than 90% reduction in new active MRI lesions.
- ASCLEPIOS I - ofatumumab compared to Aubagio (teriflunomide)
- ASCLEPIOS II - ofatumumab compared to Aubagio (teriflunomide)
These phase III studies involved 1,882 people with relapsing remitting MS. Participants took either ofatumumab by subcutaneous injections every four weeks or Aubagio (teriflunomide) once daily for up to 2.5 years. In both studies, relapse rates were significantly lower for those taking ofatumumab. For the groups taking ofatumumab, the annual relapse rates were 0.11 and 0.10, a reduction of 50-59% compared to Aubagio. Ofatumumab also significantly reduced disability worsening which remained for 3 months and 6 months by 34% and 32% respectively. There was an indication that those taking ofatumumab were more likely to have an improvement in disability levels, although this was not statistically significant.
In clinical trials, the most frequent side effects have been injection related reactions. Most of these were mild to moderate, cleared up the same or following day and were associated with the first ofatumumab injection; they were less frequent with subsequent injections. Other side effects that affected at least 10% of people taking ofatumumab were head colds, headache, chest infections and urinary tract infections.
- Neurology 2014;82:573-581. Summary Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: A phase 2 study.
- Neurology 2018 May 15;90(20):e1805-e1814. Full article Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study.
- Phase III ASCLEPIOS trials demonstrate robust efficacy of ofatumumab in patients with relapsing multiple sclerosis Novartis press release - 13 September 2019 Read online
- New England Journal of Medicine 2020; 383:546-57 Summary Ofatumumab versus teriflunomide in multiple sclerosis.
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