“These results confirm that fingolimod is generally well tolerated,” the researchers reported. “The 0.5-mg dose was generally better tolerated than the 1.25-mg dose, [and was] associated with fewer bradycardia and serious adverse events and no cases of macular edema.”
—Rebecca K. Abma
Suggested Reading
Cohen JA, Barkhof F, Comi G, et al; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402-415.
Kappos L, Radue EW, O’Connor P, et al; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387-401.
More Oral MS Drugs in the Pipeline
TORONTO—A number of other oral MS drugs are also in development and were reported on at the 62nd Annual Meeting of the American Academy of Neurology.
Cladribine, an adenosine deaminase-resistant purine nucleoside that targets CD4+ T cells and spares B cells and natural killer cells, is taken as short cycles (once daily for five days), which are then repeated monthly for a total of two (3.5-mg/kg) or four (5.25-mg/kg) cycles in the first year and two cycles in the second year. In the 96-month Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study of 1,326 patients with relapsing-remitting MS, Gavin Giovannoni, PhD, Chair of Neurology, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry and the Department of Neurology, Barts and The London NHS Trust, reported that treatment with cladribine in either 3.5-mg/kg or 5.25-mg/kg doses offered significant treatment benefits over placebo, with consistent reductions in the annualized relapse rate and decreases in health care costs. When examining the data for complete disease remission, the investigators found that 71.8% of patients taking 3.5 mg and 70.4% of those taking 5.25 mg were relapse- and disease-progression free, compared with 52.6% of the placebo group. When the third end point of MRI-activity was added, 43.0% of the 3.5-mg group and 44.3% of the 5.25-mg group were disease-activity free, compared with 16% of the placebo group. Cladribine developer Merck Serono SA, Geneva, Switzerland, was issued a refuse to file letter from the FDA late last year.
Teriflunomide, an FDA-approved arthritis treatment from Sanofi-Aventis, Bridgewater, New Jersey, is currently in phase III trials for relapsing-remitting MS. Research presented at the conference noted, “the immunomodulatory effects of teriflunomide are associated with a reduction in the infiltration of macrophages, B cells, and T cells, and an increased survival of oligodendrocytes in the spinal cord. Therefore, teriflunomide treatment could potentially delay neurodegeneration in MS by preventing the loss of myelin and oligodendrocytes.” A six-month, placebo-controlled study of teriflunomide combined with glatiramer acetate found that both 7-mg and 14-mg daily doses improved disease control as measured by MRI scans compared to placebo.
BG-12 is oral dimethyl fumarate taken two to three times a day. Researchers suspect that it may act via the nuclear factor-E2–related factor 2 (Nrf2) transcription pathway. Biogen Idec, Inc, Cambridge, Massachusetts, is conducting two large, phase III trials: Determination of the Efficacy and Safety of Oral Fumarate in Relapsing Remitting MS (DEFINE), a randomized, double-blind, placebo-controlled study of 1,237 patients; and Comparator and an Oral Fumarate in Relapsing Remitting Multiple Sclerosis (CONFIRM), a randomized, double-blind, placebo-controlled and active reference (glatiramer acetate) trial of 1,431 patients.
BAF312, a second-generation S1P receptor modulator, from Novartis Pharma, Basel, Switzerland, selectively targets S1P1 and S1P5 receptors, and is currently in phase II trials. Researchers reported that BAF312 “reverses chronic neurologic paralysis and reduces inflammation and demyelination in EAE mice, and thus may represent a promising treatment modality for inflammatory autoimmune diseases like MS.”
—Rebecca K. Abma
Suggested Reading
Rammohan KW, Shoemaker J. Emerging multiple sclerosis oral therapies. Neurology. 2010;74(Suppl 1):S47-S53.