News Briefs from ECTRIMS Meeting

October 2006

The 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) was recently held in Madrid, Spain. Taking place from September 27th through September 30th, this annual meeting provides the latest in MS information to neurologists and other medical professionals from around the world. MSAA’s Vice President and Chief Medical Officer Dr. Jack Burks was in attendance. He returned to MSAA with much news about currently approved MS medications, as well as investigative drugs showing potential in clinical studies. To follow is a brief overview of a few topics that were presented at the meeting.

News Regarding Some of the Currently Approved MS Medications

Betaseron: Berlex’s 16-year follow-up study, which is the longest follow-up study for any disease-modifying therapy in MS, continues to show positive results for individuals taking Betaseron® over the course of several years. Data shows long-term effectiveness, safety, and tolerability in MS.
    Results of the 16-year follow-up study show that individuals with relapsing forms of MS experience an average of up to 40 percent fewer relapses per year (than those not taking the drug) over a 16-year time period. Individuals who remain on Betaseron also have slower disease progression as compared to those not taking the drug, nearly doubling the time (from seven years to 13 years) before reaching an EDSS level of 6.0 (at which time one needs assistance with walking). Additionally, no new or unexpected adverse events were observed.
    Since the ECTRIMS meeting, Berlex announced that the United States Food and Drug Administration (FDA) had expanded the indication for Betaseron. As of October 2006, Betaseron may now be prescribed for individuals experiencing a first event suggestive of MS (and prior to the diagnosis of MS). A two-year study named BENEFIT (Betaseron in Newly Emerging MS for Initial Treatment) showed that early treatment with Betaseron delayed the time to a second clinical event by one year when compared to those taking a placebo.

Rebif: One-year data from an ongoing two-year study show that a new formulation of Rebif® (interferon beta-1a) is better tolerated than the presently approved formulation. When compared to an earlier trial (known as the EVIDENCE study), the percentage of those who were positive for neutralizing antibodies (NAbs) at 48 weeks was reduced by nearly half, going from 24.4 percent during the first study, to 13.9 percent at the same time with the second study using the new formulation. Persistent NAbs were observed in 14.3 percent of the participants in the first study at 48 weeks, but only 2.5 percent of the study participants taking the new formulation were found to have persistent NAbs.
    Additionally, injection-site reactions were reduced by nearly two thirds, going from 83.8 percent during the first study to 29.6 percent during the second study with the new formulation of Rebif. More information will become available as the two-year study is completed.

Copaxone: A new study shows that while antibodies to Copaxone® (glatiramer acetate injection) develop in all patients treated with the drug, these antibodies do not interfere with Copaxone’s effectiveness. Over a mean period of more than six years, patients in this study who were continuously treated with Copaxone experienced only a minimal increase in their EDSS score, indicating that the long-term efficacy of the drug was not compromised by treatment-related antibodies.
Another new study showed that patients with very active MS may benefit from a combination therapy of Novantrone® (mitoxantrone) followed by Copaxone therapy alone. Those who first received short-term induction treatment with Novantrone® (mitoxantrone), and then followed-up with Copaxone therapy alone, experienced an 89 percent reduction in disease activity as measured by Magnetic Resonance Imaging (MRI), compared to patients taking only Copaxone from the start. This initial benefit was achieved early on and was maintained throughout the 15-month study period. No adverse events outside of those associated with either treatment (when either is used as a monotherapy) were observed.
    A third study showed significant and sustained efficacy of Copaxone alone, following the short-term combination therapy with intravenous (IV) steroids for individuals with highly active MS disease activity (as shown by baseline MRI scans). Participants who first received combination therapy for six months with IV steroids and Copaxone injections, followed by treatment with Copaxone alone, experienced a 65-percent reduction in lesions. This reduction was observed during the first six months of the study, and was sustained for an additional six-month period while patients received Copaxone treatment alone. This was an open-label, one-arm study, however, which did not include a placebo (or “control”) group.

News Regarding Some of the Investigational Drugs Still in Clinical Trials

FTY720: The investigational drug known as “FTY720” (fingolimod) is a once-daily oral therapy being studied for the treatment of relapsing forms of MS. Data from a Phase II study show that up to 77 percent of patients taking the drug remained free of relapses for more than two years. They also maintained a low rate of inflammatory disease as measured by MRI. FTY720 showed minimal toxicity (adverse events) in this study.
    New data suggest that FTY720 may work through more than one mode of action. First, this drug reversibly traps a portion of circulating lymphocytes in the lymph nodes. These cells, also known as T-cells, are believed to attack the myelin and nerves of the central nervous system (CNS), causing the symptoms of MS. FTY720 lowers the number of T-cells circulating in the bloodstream and the CNS. Second, this drug reduces the permeability of the blood-brain barrier, allowing fewer damaging cells to cross from the bloodstream and into the CNS. Third, FTY720 may also have the potential to reduce neurodegeneration, enhancing nerve repair (this effect was observed in animal studies).
    A large-scale program of Phase III clinical trials to study FTY720 began earlier this year. This includes a Phase III clinical trial program known as FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis). This two-year study is designed to include more than 2,000 patients worldwide between the ages of 18 and 55, with the relapsing-remitting form of MS. For more information about the study, including eligibility criteria and study locations, readers may call (866) 788-3930, or visit www.msclinicaltrials.com.

MBP8298: Results from the completed Phase II trial, long-term follow-up treatment and current status of the ongoing pivotal Phase II/III clinical trial, as well as future clinical development plans, were presented at the ECTRIMS meeting. According to BioMS (developers of the drug), MBP8298 safely delayed disease progression for five years in progressive MS patients who had certain immune-response gene types. Approximately 75 percent of the total MS population has these gene types.
    Treatment and follow-up demonstrated that patients in the gene-responder group had a median time to disease progression of 78 months (six-and-a-half years) compared to 18 months (one-and-a-half years) for patients who received a placebo. MBP8298 is typically administered intravenously every six months. The current Phase II/III clinical trial is being conducted with secondary-progressive patients at study locations throughout Canada and Europe. For more information, readers may visit the BioMS website at www.biomsmedical.com, or call (866)701-6033.

Oral Cladribine: A few days before the ECTRIMS meeting was held, Serono announced that oral cladribine had been designated as a “Fast Track” product by the FDA, for patients with relapsing forms of MS. Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions. They must also demonstrate the potential to address unmet medical needs.
    This oral formulation of cladribine is currently being evaluated in a multi-center, multi-national Phase III study, known as CLARITY (CLAdRIbine Tablets Treating MS OrallY). Patient enrollment for this two-year, double-blind, placebo-controlled study is planned to be completed by the end of the year. Currently, recruitment is taking place in 15 cities across the United States. Further clinical trial site information is available at www.TheCLARITYStudy.com, or the U.S. National Institutes of Health clinical trial information website at www.clinicaltrials.gov. Readers without internet access may call MSAA's toll-free Helpline (800) 532-7667.

Campath: Two-year interim results from its three-year Phase II trial have been presented for Campath® (alemtuzumab), which compares the effectiveness and safety of Campath to Rebif. Dosing of Campath in the study was suspended in September 2005 after three patients developed immune thrombocytopenic purpura (ITP). This is a treatable but serious condition in which patients experience a low platelet count from an immune response against the platelets, which can cause excessive bleeding. The first patient to present with ITP died. The other two patients, along with three more who have since been diagnosed with ITP, all underwent treatment for ITP and responded well.
    At that time, most patients had received two cycles (each given once per year). Treatment with Rebif continued without interruption. Analysis showed that patients taking either a high or low dose of Campath experienced at least a 75-percent reduction in the risk for relapse after at least two years when compared to the Rebif-treated group. Participants in the Campath group also experienced at least a 65-percent reduction in the risk for progression of clinically significant disability compared to the Rebif-treated group.
    Additionally, previous studies with Campath and MS have shown a connection between Campath and thyroid problems, including Graves’ disease. Campath works by destroying the body's T-cells, which are believed to be responsible for the damage to the myelin and nerves with MS.

BG00012: BG00012 is an oral drug that is an effective treatment for chronic plaque psoriasis. A preliminary study indicated that BG00012 may also be effective in patients with relapsing-remitting MS. This drug has an immunomodulatory mechanism of action.
    This randomized, double-blinded, placebo-controlled Phase 2b study was conducted with patients who had relapsing-remitting MS. The study compared a placebo group and three groups taking different doses of BG00012 to see which dose level was the most effective with the least side effects. Compared to placebo, treatment with the highest dose experienced a 69-percent reduction in the total number of gadolinium-enhanced lesions and a reduction in the number of new and enlarging, T1 and T2-hyperintense lesions over a 24-week period. A 32-percent reduction in relapse rate was also observed, but since this endpoint was not included in the study design, it could not be considered significant.

By Susan Wells Courtney
Reviewed by Dr. Jack Burks

Please note: The information given in this article was obtained through MSAA resources, ECTRIMS news releases, as well as statements from the drug companies whose approved medications or investigational drugs were highlighted.

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The most common neurological disorder diagnosed in young adults, multiple sclerosis is an autoimmune disease of the central nervous system. This disorder damages or destroys the protective covering (known as myelin) surrounding the nerves, causing reduced communication between the brain and nerve pathways. Common symptoms include visual problems, overwhelming fatigue, difficulty with balance and coordination, and various levels of impaired mobility. MS is not contagious or fatal.

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