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TORONTO—Annualized relapse rates in patients with relapsing-remitting multiple sclerosis (MS) were more than 50% lower in subjects taking oral fingolimod (FTY720) than in those taking a placebo, according to research presented at the 62nd Annual Meeting of the American Academy of Neurology. The medication also reduced the risk of disability progression by 30% and significantly decreased the number of new or enlarged T2 lesions and gadolinium-enhancing lesions, per 24-month results of the phase III FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial.
Oral fingolimod, a sphingosine 1-phosphate receptor (S1PR) modulator, is the first in a novel class of drugs under evaluation for the treatment of relapsing and progressive forms of MS. S1PR modulators work to retain circulating lymphocytes in the lymph nodes, thereby reducing the recirculation of autoreactive lymphocytes and preventing penetration of these lymphocytes into the CNS.
Fingolimod Versus Placebo
The double-blind, placebo-controlled multicenter FREEDOMS study randomized 1,083 patients (mean age, 40.5) to receive once-daily doses of either 1.25-mg fingolimod, 0.5-mg fingolimod, or a placebo. For the primary end point of annualized relapse rate, both doses of fingolimod were superior to placebo, with a 54% reduction in relapses for the lower dose and a 60% reduction in the higher dose. For the key secondary end point of time to three-month confirmed disability progression, measured by a 1-point increase in the Expanded Disability Status Scale (EDSS), a 30% risk reduction was reported in the 0.5-mg dose, and 32% in the 1.25-mg dose, compared with placebo.
“Overall, 1.25-mg fingolimod did not offer any advantages regarding efficacy, and it had a slightly higher array of side effects; therefore, 0.5 mg is the dosage that we will submit an application for [FDA] approval at this time,” announced Ludwig Kappos, MD, of the Department of Neurology, University Hospital, University of Basel, Switzerland.
The second phase of the study, which was presented in 2006, showed a “clear cut effect on inflammatory outcomes on MRI,” Dr. Kappos noted. “Five years of follow-up support these effects…. Approximately 99.5% of patients remaining in the study do not show MRI activity and have a low annualized relapse rate at approximately 0.2, [which is equivalent to] one relapse every five years.”
The phase III, 24-month MRI inflammatory activity results favored fingolimod over placebo, with 50.5% of the 0.5-mg fingolimod group and 51.9% of the 1.25-mg group free from new or newly enlarged T2 lesions, compared with 21.2% of the placebo group, reported Ernst-Wilhelm Radue, MD, Director of Medical Image Analysis Center, University Hospital Basel, Switzerland. In addition, more patients were free from gadolinium-enhanced lesions with fingolimod (89.7% and 89.8%), compared with placebo (65.1%).
Fingolimod Versus Interferon
A second study, the Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS), compared both doses of fingolimod to intramuscular interferon beta-1a and found that the oral medicine reduced annualized relapse rates by up to 50%, compared with injectable interferon.
The 12-month phase III study of 1,153 patients also found that fewer patients experienced relapses requiring steroid treatment and/or hospitalization when treated with fingolimod than when treated with interferon beta-1a. Patients in both fingolimod groups also had significantly less deterioration of the ability to perform daily activities, based on the Patient-Reported Indices for Multiple Sclerosis (PRIMUS)–Activities scores, compared with the interferon group.
A 24-month optional extension study to assess the safety and efficacy—both clinically and on MRI—is under way and involves 89% of the patients who completed the core TRANSFORMS study. Patients who were taking weekly interferon beta-1a injections have been switched to daily oral fingolimod, and those who took fingolimod in the earlier phase of the trial have continued on the medication. Following the results of the FREEDOMS II trial, all subjects in the TRANSFORMS extension study are taking the 0.5-mg dose.
Safety and Tolerability
Of the 1,272 patients initially enrolled in the FREEDOMS trial, 81% completed the study. Those who discontinued the trial were proportionately lower in the 0.5-mg fingolimod group (19%), compared with the 1.25-mg dose (31%) or placebo (28%) groups.
The percentages of patients reporting any adverse events were similar for both fingolimod groups (94%) and placebo (93%). Serious adverse events were reported in 10% of patients taking 0.5-mg fingolimod, 12% of those taking 1.25-mg fingolimod, and 13% of the placebo group. Serious infectious adverse events occurred in 1.6% of the 0.5-mg group, 2.6% of the 1.25-mg group, and 1.9% of the placebo group.
Malignant neoplasms were reported in 10 patients in the placebo group and four patients in each active group. Seven cases of macular edema occurred, all in patients on the 1.25-mg dose. A transient heart rate decrease at the beginning of treatment, minor increases in blood pressure, and increases in liver enzymes were also observed.
“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.
TORONTO—Annualized relapse rates in patients with relapsing-remitting multiple sclerosis (MS) were more than 50% lower in subjects taking oral fingolimod (FTY720) than in those taking a placebo, according to research presented at the 62nd Annual Meeting of the American Academy of Neurology. The medication also reduced the risk of disability progression by 30% and significantly decreased the number of new or enlarged T2 lesions and gadolinium-enhancing lesions, per 24-month results of the phase III FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial.
Oral fingolimod, a sphingosine 1-phosphate receptor (S1PR) modulator, is the first in a novel class of drugs under evaluation for the treatment of relapsing and progressive forms of MS. S1PR modulators work to retain circulating lymphocytes in the lymph nodes, thereby reducing the recirculation of autoreactive lymphocytes and preventing penetration of these lymphocytes into the CNS.
Fingolimod Versus Placebo
The double-blind, placebo-controlled multicenter FREEDOMS study randomized 1,083 patients (mean age, 40.5) to receive once-daily doses of either 1.25-mg fingolimod, 0.5-mg fingolimod, or a placebo. For the primary end point of annualized relapse rate, both doses of fingolimod were superior to placebo, with a 54% reduction in relapses for the lower dose and a 60% reduction in the higher dose. For the key secondary end point of time to three-month confirmed disability progression, measured by a 1-point increase in the Expanded Disability Status Scale (EDSS), a 30% risk reduction was reported in the 0.5-mg dose, and 32% in the 1.25-mg dose, compared with placebo.
“Overall, 1.25-mg fingolimod did not offer any advantages regarding efficacy, and it had a slightly higher array of side effects; therefore, 0.5 mg is the dosage that we will submit an application for [FDA] approval at this time,” announced Ludwig Kappos, MD, of the Department of Neurology, University Hospital, University of Basel, Switzerland.
The second phase of the study, which was presented in 2006, showed a “clear cut effect on inflammatory outcomes on MRI,” Dr. Kappos noted. “Five years of follow-up support these effects…. Approximately 99.5% of patients remaining in the study do not show MRI activity and have a low annualized relapse rate at approximately 0.2, [which is equivalent to] one relapse every five years.”
The phase III, 24-month MRI inflammatory activity results favored fingolimod over placebo, with 50.5% of the 0.5-mg fingolimod group and 51.9% of the 1.25-mg group free from new or newly enlarged T2 lesions, compared with 21.2% of the placebo group, reported Ernst-Wilhelm Radue, MD, Director of Medical Image Analysis Center, University Hospital Basel, Switzerland. In addition, more patients were free from gadolinium-enhanced lesions with fingolimod (89.7% and 89.8%), compared with placebo (65.1%).
Fingolimod Versus Interferon
A second study, the Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS), compared both doses of fingolimod to intramuscular interferon beta-1a and found that the oral medicine reduced annualized relapse rates by up to 50%, compared with injectable interferon.
The 12-month phase III study of 1,153 patients also found that fewer patients experienced relapses requiring steroid treatment and/or hospitalization when treated with fingolimod than when treated with interferon beta-1a. Patients in both fingolimod groups also had significantly less deterioration of the ability to perform daily activities, based on the Patient-Reported Indices for Multiple Sclerosis (PRIMUS)–Activities scores, compared with the interferon group.
A 24-month optional extension study to assess the safety and efficacy—both clinically and on MRI—is under way and involves 89% of the patients who completed the core TRANSFORMS study. Patients who were taking weekly interferon beta-1a injections have been switched to daily oral fingolimod, and those who took fingolimod in the earlier phase of the trial have continued on the medication. Following the results of the FREEDOMS II trial, all subjects in the TRANSFORMS extension study are taking the 0.5-mg dose.
Safety and Tolerability
Of the 1,272 patients initially enrolled in the FREEDOMS trial, 81% completed the study. Those who discontinued the trial were proportionately lower in the 0.5-mg fingolimod group (19%), compared with the 1.25-mg dose (31%) or placebo (28%) groups.
The percentages of patients reporting any adverse events were similar for both fingolimod groups (94%) and placebo (93%). Serious adverse events were reported in 10% of patients taking 0.5-mg fingolimod, 12% of those taking 1.25-mg fingolimod, and 13% of the placebo group. Serious infectious adverse events occurred in 1.6% of the 0.5-mg group, 2.6% of the 1.25-mg group, and 1.9% of the placebo group.
Malignant neoplasms were reported in 10 patients in the placebo group and four patients in each active group. Seven cases of macular edema occurred, all in patients on the 1.25-mg dose. A transient heart rate decrease at the beginning of treatment, minor increases in blood pressure, and increases in liver enzymes were also observed.
“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.
TORONTO—Annualized relapse rates in patients with relapsing-remitting multiple sclerosis (MS) were more than 50% lower in subjects taking oral fingolimod (FTY720) than in those taking a placebo, according to research presented at the 62nd Annual Meeting of the American Academy of Neurology. The medication also reduced the risk of disability progression by 30% and significantly decreased the number of new or enlarged T2 lesions and gadolinium-enhancing lesions, per 24-month results of the phase III FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial.
Oral fingolimod, a sphingosine 1-phosphate receptor (S1PR) modulator, is the first in a novel class of drugs under evaluation for the treatment of relapsing and progressive forms of MS. S1PR modulators work to retain circulating lymphocytes in the lymph nodes, thereby reducing the recirculation of autoreactive lymphocytes and preventing penetration of these lymphocytes into the CNS.
Fingolimod Versus Placebo
The double-blind, placebo-controlled multicenter FREEDOMS study randomized 1,083 patients (mean age, 40.5) to receive once-daily doses of either 1.25-mg fingolimod, 0.5-mg fingolimod, or a placebo. For the primary end point of annualized relapse rate, both doses of fingolimod were superior to placebo, with a 54% reduction in relapses for the lower dose and a 60% reduction in the higher dose. For the key secondary end point of time to three-month confirmed disability progression, measured by a 1-point increase in the Expanded Disability Status Scale (EDSS), a 30% risk reduction was reported in the 0.5-mg dose, and 32% in the 1.25-mg dose, compared with placebo.
“Overall, 1.25-mg fingolimod did not offer any advantages regarding efficacy, and it had a slightly higher array of side effects; therefore, 0.5 mg is the dosage that we will submit an application for [FDA] approval at this time,” announced Ludwig Kappos, MD, of the Department of Neurology, University Hospital, University of Basel, Switzerland.
The second phase of the study, which was presented in 2006, showed a “clear cut effect on inflammatory outcomes on MRI,” Dr. Kappos noted. “Five years of follow-up support these effects…. Approximately 99.5% of patients remaining in the study do not show MRI activity and have a low annualized relapse rate at approximately 0.2, [which is equivalent to] one relapse every five years.”
The phase III, 24-month MRI inflammatory activity results favored fingolimod over placebo, with 50.5% of the 0.5-mg fingolimod group and 51.9% of the 1.25-mg group free from new or newly enlarged T2 lesions, compared with 21.2% of the placebo group, reported Ernst-Wilhelm Radue, MD, Director of Medical Image Analysis Center, University Hospital Basel, Switzerland. In addition, more patients were free from gadolinium-enhanced lesions with fingolimod (89.7% and 89.8%), compared with placebo (65.1%).
Fingolimod Versus Interferon
A second study, the Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS), compared both doses of fingolimod to intramuscular interferon beta-1a and found that the oral medicine reduced annualized relapse rates by up to 50%, compared with injectable interferon.
The 12-month phase III study of 1,153 patients also found that fewer patients experienced relapses requiring steroid treatment and/or hospitalization when treated with fingolimod than when treated with interferon beta-1a. Patients in both fingolimod groups also had significantly less deterioration of the ability to perform daily activities, based on the Patient-Reported Indices for Multiple Sclerosis (PRIMUS)–Activities scores, compared with the interferon group.
A 24-month optional extension study to assess the safety and efficacy—both clinically and on MRI—is under way and involves 89% of the patients who completed the core TRANSFORMS study. Patients who were taking weekly interferon beta-1a injections have been switched to daily oral fingolimod, and those who took fingolimod in the earlier phase of the trial have continued on the medication. Following the results of the FREEDOMS II trial, all subjects in the TRANSFORMS extension study are taking the 0.5-mg dose.
Safety and Tolerability
Of the 1,272 patients initially enrolled in the FREEDOMS trial, 81% completed the study. Those who discontinued the trial were proportionately lower in the 0.5-mg fingolimod group (19%), compared with the 1.25-mg dose (31%) or placebo (28%) groups.
The percentages of patients reporting any adverse events were similar for both fingolimod groups (94%) and placebo (93%). Serious adverse events were reported in 10% of patients taking 0.5-mg fingolimod, 12% of those taking 1.25-mg fingolimod, and 13% of the placebo group. Serious infectious adverse events occurred in 1.6% of the 0.5-mg group, 2.6% of the 1.25-mg group, and 1.9% of the placebo group.
Malignant neoplasms were reported in 10 patients in the placebo group and four patients in each active group. Seven cases of macular edema occurred, all in patients on the 1.25-mg dose. A transient heart rate decrease at the beginning of treatment, minor increases in blood pressure, and increases in liver enzymes were also observed.
“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.