Ocrelizumab: MS Drug in the Pipeline

Emerging MS therapy for Relapsing and Primary-Progressive MS

Nurse injecting medicine into IV bag
Ocrelizumab: An MS Drug in the Pipeline. Echo/Getty Images

Have you heard of the monoclonal antibody ocrelizumab that is being studied to treat both primary progressive MS and relapsing types of MS?

While it is not yet approved by the United Stated Food and Drug Administration (FDA), it's sensible to get the early bird insight into the science behind this medication.

This way you have a solid knowledge base if ocrelizumab ever becomes an option for your MS care.

What Is Ocrelizumab?

Ocrelizumab is a humanized monoclonal antibody that selectively binds to a molecule called CD20, which lies on the surface of B cells (a type of immune system cell). By binding to CD20, the number of B cells is decreased in a person's bloodstream.

Since B cells play a role in myelin sheath loss and damage in multiple sclerosis, depleting these particular B cells has been shown to reduce MS disease activity. That being said, because ocrelizumab only targets B cells, other cells within the immune system (like T cells) remain intact, helping to maintain a person's immune function.

Ocrelizumab in Phase III Trials MS

Ocrelizumab was examined in three phase III trials for treating both relapsing MS and primary progressive MS. For relapsing MS, ocrelizumab was compared to Rebif. Since there is currently no FDA-approved medication for primary-progressive MS, ocrelizumab was compared to placebo in that trial.

A little reminder—while phase II trials examine the safety and benefit of a drug, phase III trials are larger and compare the drug to the standard of care drug.

Treating Relapsing MS With Ocrelizumab

In the two phase III trials of people with relapsing MS, over 1600 participants were randomized to receive either ocrelizumab infusion every six months or Rebif (interferon beta-1a) three times weekly for 96 weeks (nearly two years).

Rebif is a subcutaneous injection, meaning it is given underneath the skin with a thin needle.

Results revealed that the yearly relapse rate was 46 to 47 percent lower in the participants who received ocrelizumab than in the participants who received Rebif.  In addition, the progression of the participants' disability was measured at both 12 weeks and 24 weeks using the EDSS scale.

In both time frames, the participants who received ocrelizumab had lower disability progression than those who received Rebif.

Also, there were 94 to 95 percent less gadolinium-enhancing lesions on MRI in the ocrelizumab group than the Rebif group.

Adverse effects in these two trials included:

  • Infusion-related reactions in the ocrelizumab group (in a little over a third of the participants): like rash, flushing, or itchiness
  • Serious infections occurred in 1.3 percent of those in the ocrelizumab group and 2.9 percent in the Rebif group
  • New, abnormal tissue growths (called neoplasms) occurred in 0.5 percent of those in the ocrelizumab group and 0.2 percent in the Rebif group.

Treating Primary-Progressive MS With Ocrelizumab

In a phase III trial of ocrelizumab in primary-progressive MS (PPMS), over 700 participants received either ocrelizumab or a placebo infusion every 6 months for at least 120 weeks.

Results revealed that at 12 weeks, 33 percent of the participants who received ocrelizumab had confirmed disability progression, as opposed to 39 percent of those who received the placebo infusion. At 24 weeks, the confirmed disability progression was almost 30 percent in the ocrelizumab group versus almost 36 percent in the placebo group.

Ocrelizumab was also found to decrease the time it took for participants to walk 25 feet by nearly 30 percent, when compared to the placebo infusion.

On brain MRI, after 120 weeks, there was 3.4 percent less total volume of T2-hyperintense brain lesions in the ocrelizumab group versus 7.4 percent more lesions in the placebo group.

In terms of adverse effects, the ocrelizumab group had more infusion-related reactions, upper respiratory tract infections, and oral herpes infections. The infusion-related reactions (like rash, itching, flushing, and throat irritation) were more common after the first infusion and improved with next doses.

Serious infections occurred in 6.2 percent of the ocrelizumab group and 5.9 percent of the placebo group—so similar in both groups. The researchers carefully defined what a serious infection was—an infection that was fatal, life-threatening, required hospitalization, resulted in disability, or required medical intervention (like intravenous antibiotics) to prevent death or disability.

It's interesting to note that there were more neoplasms in the ocrelizumab group than the placebo group (2.3 percent versus 0.8 percent). It's unclear why this is the case and warrants further investigation.

A Word From Verywell

There are currently no FDA-approved medications to treat primary progressive MS. So the approval of ocrelizumab is extremely exciting for this population (about 10 to 15 percent of people with MS are diagnosed with the primary-progressive type). Of course, it is exciting too for those with relapsing types of MS, as many people have continued to develop relapses despite current MS treatments.

This all being said, ocrelizumab is not currently FDA approved. The safety, especially the long-term risks associated with this drug, need to be evaluated. Still, this potential therapy gives us hope—and that is all many of us need right now.

Sources:

Hauser SL et al. Ocrelizumab versus Interferon Beta-1a in relapsing multiple sclerosis. N Engl J Med. 2016 Dec 21.

Montalban X et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2016 Dec 21.

Sorensen PS, Blinkenberg M. The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord. 2016 Jan;9(1):44-52.

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