Medicine & Research

MS Drugs in the Pipeline: Focus on Progressive Form

By Ellen Whipple Guthrie, Pharm.D.

Eighty-five percent of people with multiple sclerosis are originally diagnosed with a relapsing-remitting course of the disease (RRMS). Characterized by a pattern of attacks followed by remissions, RRMS is often treated with first line disease-modifying drugs such as Avonex®, Betaseron®, Copaxone®, and Rebif® (which are frequently referred to as the ABCR drugs), or with Tysabri®. There is a growing consensus that treatment should begin as soon as possible after a diagnosis of RRMS and that the therapy should continue indefinitely, except in the event of a clear lack of benefit, intolerable adverse effects, new data, or better therapies.

Sometimes, over the years a person with RRMS will develop a more progressive course of the disease, with or without occasional relapses, known as secondary progressive MS (SPMS). Others experience constant disease progression from the very beginning, characterized by a slow but nearly continuous worsening of the disease with no distinct relapses or remissions. This is known as primary progressive MS (PPMS). In these cases, the treatment options are not as clear cut.

An ABCR drug or Tysabri can be used to treat people with SPMS if they are still experiencing relapses. Another option, Novantrone®, is also approved by the U.S. Food and Drug Administration to treat people with the condition. And, although they are not specifically approved by the FDA for use in MS, the chemotherapies methotrexate and cyclophosphamide frequently are used, as well.

Treating PPMS is much more challenging; to date, no therapy has shown convincing evidence of slowing its disease progression. However, that does not mean that an effective treatment will not emerge in the future. At this time, several experimental medications are being studied for use in people with PPMS and SPMS, including: 

Teriflunomide – This product blocks T-cells from crossing the blood-brain barrier and damaging the central nervous system. As an oral medication being studied in people with SPMS, teriflunomide has shown great promise in recent clinical trials.

In 2006, two different dosing levels of teriflunomide were compared to placebo. Interestingly, both doses studied were associated with reduced numbers of active MRI lesions. In addition, the people who received the higher dose of this drug did better with regard to disability. A larger study with participants from all over the world, called TEMSO, is currently underway, but is no longer recruiting patients.

Dirucotide (MBP8298) – An intravenous agent administered once every six months, dirucotide is currently being researched in patients with SPMS. MS centers from 29 states are participating in this study, known as MAESTRO-03. To enroll in this clinical trial, patients must be 18 to 65 years of age, with a documented history of SPMS. Unique to this drug is the fact there is a blood test available to determine which patients may benefit from treatment.

Rituximab – Another intravenous product, rituximab has shown very mixed results in people with MS thus far. A small trial published in 2007 found it to be “highly effective” against MS. However, a larger study of patients with PPMS, published in September 2008, found that effectiveness was limited to certain patients, generally those who were younger or who had signs of inflammation on MRI, or both.

Plasmapheresis – A procedure designed to deplete blood plasma (the liquid part of the blood) without depleting the body of its blood cells, plasmapheresis has been used with some success as a treatment for progressive forms of MS. It is thought that plasmapheresis may be beneficial because it removes all the immunoglobulins and other immune substances that are suspended in plasma.

Unfortunately, studies examining plasmapheresis in people with progressive forms of MS have had mixed results. Some people benefited, others did not. Plasmapheresis also carries with it the same risks as any intravenous procedure. The risk of infection increases with the use of donor plasma, which may carry viral particles despite screening procedures.

At this time, there appears to be little evidence to support the use of plasmapheresis as a first-line treatment for SPMS or PPMS. The therapy is generally reserved for those suffering severe, acute MS attacks that don’t respond to intravenous steroids.

Bone marrow transplantation – Also called “autologous stem-cell transplantation,” bone marrow transplants are being studied in some people with PPMS. Those who undergo this type of therapy have some of their bone marrow removed and treated. Next, they undergo high-dose chemotherapy and radiation to destroy their remaining bone marrow. They are then re-infused with the treated bone marrow.

It is important to note that bone marrow transplants carry very significant risks, including life-threatening infections, excessive bleeding, and death. A small number of people with PPMS have undergone this treatment and seen good results. This is most often true for younger, less disabled people. However, other people with MS who have had bone marrow transplants have seen their MS return and found that their disease course was more progressive. Some people with MS have also died from complications involved with this procedure.

You can find information about clinical trials now being conducted by visiting, an interactive online database managed by the National Library of Medicine that provides information about both federally and privately supported clinical research in human volunteers.

Ellen Guthrie received her doctorate of pharmacy degree from the University of Georgia College of Pharmacy in 1994 and has been a medical advisor with the MSF since 2002. She is an Assistant Clinical Professor at the University of Georgia College of Pharmacy, where she lectures primarily on MS. Currently she practices pharmacy at Children’s Healthcare of Atlanta, where she is a pediatric pharmacist. She is a member of the American Pharmaceutical Association, the Atlanta Academy of Institutional Pharmacists, and the Consortium of MS Centers.

(Last reviewed 7/2009)