Infusion bottle with IV solution in hospital
January 30, 2014 | News | MS ResearchMS Treatments

Novel multiple sclerosis treatment reports first results

The first study of a new MS therapy in development has found that the drug, ofatumumab, appears to be highly effective in reducing new inflammatory lesions in the brain (Sorensen and colleagues. Neurology 2014; epublished January 22, 2014). The drug was developed by a Danish company, Genmab, and licensed to GlaxoSmithKline. It’s currently available in some countries (as Arzerra) to treat a type of leukemia.


Ofatumumab is a monoclonal antibody (MAb), a technology that allows a drug to specifically target one of the body’s proteins. Tysabri (natalizumab) and Lemtrada (alemtuzumab) are two other MAbs that are currently being used to treat MS.

MS is generally considered to be a dysregulated immune response that is largely driven by immune cells called T cells, and the current crop of MS medications modulate the T cell response in one way or another.

Ofatumumab has a different approach. It targets a protein found on a different population of immune cells called B cells. This is a new avenue of research in MS and a number of drugs that target B cells (rituximab, ocrelizumab) have been studied to see if this way of combatting MS is effective.

B cells have two key roles in the immune response that may be important in MS. When they encounter a foreign invader (such as a virus) they produce antibodies, which help destroy the invader. They can also “present” what they find to T cells, which starts the process of T cell activation. This process works both ways – activated T cells can also turn on B cells to produce antibodies. So B cells and T cells work as a tag team, together driving the inflammatory response that is the key feature of MS (and which shows up as MRI lesions and relapses).

Like other MAbs, ofatumumab is administered by infusion (a slow drip into the vein). In the phase II study, 38 people received one of three doses of the drug or a placebo, followed by a second dose two weeks later. This was a crossover study so the two groups switched places at the six-month mark. Those in the treatment group received placebo, and those in the placebo group got the active drug.

Overall, new inflammatory lesions (as seen on MRI) were reduced 99%, an impressive achievement. The effect of the drug on relapses wasn’t examined. Infusion reactions were common, but otherwise the drug appeared to be well tolerated.

However, some safety concerns have been raised about all of the B cell drugs. Because of ofatumumab’s suppressive effects on the immune system, the FDA has cautioned about the risk of hepatitis virus reactivation (when it’s used as a leukemia treatment) in people with hepatitis B ( There have also been cases of PML (progressive multifocal leukoencephalopathy) with ofatumumab, which has been such a problem for Tysabri. However, these cases occurred with the substantially higher doses of ofatumumab used for leukemia so the PML risk with the dosing used to treat MS isn’t known. A larger phase II trial called MIRROR is expected to have preliminary results later this year.

The idea of targeting B cells in MS began several years ago with a phase II trial of rituximab (Hauser and colleagues. N Engl J Med 2008; 358:676-688). In that study, treatment also had a substantial effect on new inflammatory lesions (a 91% reduction); the relapse rate was reduced 55% at six months, but was not significantly different than placebo at one year (suggesting that a second treatment course is needed at six months). There were also promising results when rituximab was used as an add-on therapy in people who weren’t fully responding to an injectable (Naismith and colleagues. Neurology 2010;74:1860-1867). The drug was tested in primary-progressive MS in the OLYMPUS trial but (like other therapies) had little effect (Hawker and colleagues. Ann Neurol 2009;66:460-471).

Despite all these efforts, the manufacturer of rituximab decided not to pursue it in MS any further and switched its attentions to ocrelizumab, another of its B cell drugs in the pipeline. To date, one large phase II study found that ocrelizumab reduced new inflammatory lesions by 89-96%, depending on the dose (Kappos and colleagues. Lancet 2011;378:1779-1787). One  safety concern was that a person died of a systemic inflammatory response syndrome (SIRS) during the trial. SIRS causes multiple organs in the body to fail; the reasons for this reaction aren’t known. Another potential issue is infections. Ocrelizumab was also being developed for rheumatoid arthritis, but the program was suspended when some people developed fatal infections during treatment. Phase III trials are currently comparing ocrelizumab and Rebif in relapsing-remitting MS, and looking at the drug in primary-progressive MS, but results are not expected for several years.

Overall, targeting the B cell in MS seems to be a very promising strategy. But more information is needed about the risk of potentially fatal side effects – infections, PML and severe immune reactions – with these novel therapies.

Share this article
pin it!

Related Posts