Summer 2007 Research Update, Part One: FDA-Approved Medications

June 29, 2007

Numerous trials are currently being conducted to determine the safety and effectiveness of medications for the treatment of multiple sclerosis (MS). Trials include FDA-approved drugs, experimental drugs (such as oral medications, monoclonal antibodies, and other treatments), as well as various combinations of drugs and doses. This first of four updates provides a few research highlights on each of the FDA-approved drugs for MS.

Study findings and announcements are frequently reported at international medical conferences. The American Academy of Neurology (AAN) and the Consortium of MS Centers (CMSC) are examples of such groups that hold annual meetings to update medical professionals on the latest information available on disease research and treatments. Both the AAN and CMSC meetings are held each year in the spring.

To follow are highlights of some of the recent findings in the field of MS research. This is not a complete list and additional study results may be added to this list at a later time. Please note that in many instances, initial study results should be considered as preliminary. Additional studies and/or evaluations are needed before these findings may be confirmed.

For more information and specific details on these study results, please refer to MSAA’s Summer 2007 issue of The Motivator. This will be available in August and may be viewed at that time through MSAA’s website. Anyone wishing to receive a free copy of The Motivator may call MSAA’s Helpline at (800) 532-7667. Helpline consultants and information about MSAA’s programs are also available through this number.

Part I:
Research updates on FDA-approved medications for the treatment of MS

Interferon beta 1-b (Betaseron®) approved for clinically isolated syndrome; additional studies in progress; 17-year data show continued positive effects

• Administered via subcutaneous injection every other day
• The BENEFIT TRIAL is evaluating the impact of Betaseron on patients with clinically isolated syndrome (CIS), which is the initial symptom a patient reports prior to a diagnosis of MS; Betaseron was found to reduce the risk of disability (as measured by EDSS) if the patient is treated from the onset and remains on the treatment for three years; treated patients were also less likely to progress to clinically definite MS compared to placebo controls; early treatment with Betaseron for CIS has been approved by the FDA
• Using special MRI methods, the BECOME study compares Betaseron to Copaxone for individuals with relapsing-remitting multiple sclerosis (RRMS); interim analysis at 15 months showed no difference in active, gadolinium-enhanced lesions (the primary outcome); however, Betaseron-treated patients had fewer “black holes” as seen on MRI, which are thought to represent more permanent damage
• The BEYOND study is evaluating regular-dose versus double-dose Betaseron, versus Copaxone, in a three-armed trial; results are expected later this year
• Follow-up data after 17 years from Betaseron’s pivotal, placebo-controlled trial, showed continued effectiveness and safety with treatment

Interferon beta 1-a (Avonex®) studied in combination with other drug treatments; shows continued positive effects for patients with CIS

• Taken via weekly intermuscular injections
• The ACT trial evaluated Avonex in combination with (1) methotrexate (MTX), (2) intravenous methylprednisolone (IVMP), or (3) both MTX and IVMP; low enrollment required protocol modification; data showed some trends to support that adding MTX and IVMP may be helpful in patients on Avonex with continuing active disease; the combination is reported to be safe and well-tolerated
• A very small, one-year study was conducted with RRMS patients taking Avonex; pioglitazone (Actos®) (an anti-diabetic drug taken orally once per day) or a placebo was given in combination with Avonex; the addition of Actos may reduce MRI damage in RRMS patients; the treatment was well tolerated but more studies are needed
• Five-year data following initial treatment with Avonex after CIS showed continued positive effects on patients receiving Avonex from the beginning versus those initially treated with a placebo
  

Interferon beta 1-a (Rebif®) has been reformulated to reduce injection-site reactions and neutralizing antibodies; statins may block therapeutic effects; other studies in progress

• Administered through subcutaneous injections three times weekly
• New reformulation of Rebif reduces injection-site reactions by nearly two-thirds, going from 83.8 percent with the original formulation to 29.6 percent with reformulated Rebif; injection-site pain and the formation of neutralizing antibodies were also reduced
• Studied in combination with atorvastatin (Lipitor®); since previous studies suggested that statins may have a beneficial effect on MS disease activity, a trial was conducted with Rebif and Lipitor; the study found this combination resulted in an increase in MRI and clinical disease activity; statins are now believed to block the therapeutic effects of interferons, so these two drugs should not be given together at this time
• Studies are being conducted on Rebif’s effect on CIS
• A recent study comparing Rebif to Copaxone was completed; data still being analyzed

Glatiramer acetate (Copaxone®) studied in combination with other drug treatments; double-dose study encouraging; PPMS study stopped; CIS study in progress

• Given through daily subcutaneous injections
• An ongoing trial combines Copaxone with Avonex (COMBI Rx trial); three arms: Copaxone alone, Avonex alone, and combination of both
• Another study looks at Copaxone combined with minocycline (in addition to its antibiotic properties, minocycline also has an effect on the immune system); minocycline is given orally once per day; the combination reflected a consistent pattern of benefit in the reduction of new and active MRI lesions; also reported to be safe and well tolerated
• Study with a double-dose of Copaxone showed encouraging results; a larger study is planned
• A study in primary-progressive multiple sclerosis (PPMS) was stopped due to lack of effectiveness; in a subsequent analysis, a trend toward a positive effect in men was noted
• Copaxone is being tested in the treatment of CIS

Mitoxantrone (Novantrone®) helps individuals with certain types of MS; combination treatment may be helpful

• Given via intravenous injection once every three months for two to three years
• Has been shown to help people with secondary-progressive multiple sclerosis (SPMS), progressive-relapsing multiple sclerosis (PRMS), or worsening RRMS; not indicated for PPMS
• A study showed that switching to Novantrone, followed by Copaxone, may help patients who were taking Rebif and experienced continued disease activity

Natalizumab (Tysabri®) continues to show effectiveness at three years; no new cases of PML

• Administered via intravenous infusions every four weeks
• Three-year data show continued effectiveness (reduction in relapses and disability as well as favorable MRI data)
• At 10 months into progress of safety studies (TOUCH program in United States and TIGRESS program internationally), no new cases of PML found; participants continue to be monitored (PML, or Progressive Multifocal Leukoencephalopathy, is a viral disease occurring in immuno-suppressed patients)

By Susan Wells Courtney, MSAA Senior Writer and Creative Director
Reviewed by Dr. Jack Burks, MSAA Chief Medical Officer

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