News Briefs From the 28th Congress of ECTRIMS

LYON, FRANCE—The following news stories were originally written on site at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and posted on the Neurology Reviews website www.neurologyreviews.com. We have reproduced them here for readers who did not see our online conference reporting. More news from the ECTRIMS Congress can be found online and in upcoming issues of Neurology Reviews.

Postmarketing Safety Data Released for Ampyra (Dalfampridine)
Michele Jara, DSc, Director of Epidemiology at Accorda Therapeutics in Hawthorne, New Jersey, and colleagues presented the findings from a two-year safety study of Ampyra (dalfampridine) extended-release tablets (10 mg) indicated for the treatment of walking impairment in patients with multiple sclerosis (MS). Among the major findings, Dr. Jara reported that:

• The safety profile for Ampyra two years after FDA approval is similar to that observed in clinical trials.
• The most frequent associated adverse events were dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, back pain, and asthenia.
• Among the 62,400 patients prescribed Ampyra, the rate of seizure (4.6 per 1,000 patient-years of use) was comparable to that seen in the MS population overall. Length of treatment prior to seizure ranged from first dose to two years, with 20% of the seizures occurring within a week of starting treatment.

The analysis examined all postmarketing data that were reported to the drug maker (Acorda) and the FDA from March 2010 through March 2012.

Teva Announces Top-Line Data From the GALA Study—New Dosing Regimen for Glatiramer Acetate
Data from a phase III trial support the efficacy of a new dosing regimen for Copaxone (glatiramer acetate) for patients with relapsing-remitting multiple sclerosis (MS).

Teva Pharmaceutical Industries released data from the Glatiramer Acetate Low-Frequency Administration (GALA) study, which was designed to evaluate the efficacy, safety, and tolerability of 40 mg/mL of glatiramer acetate three times weekly instead of the 20-mg/mL daily subcutaneous injection that has been the recommended dose for almost two decades.

In the GALA study, a one-year, randomized, double-blind, placebo-controlled trial, glatiramer acetate 40 mg/mL injected three times weekly significantly reduced annualized relapse rates by 34.4% versus placebo. The cumulative number of new and enlarging T2 lesions was significantly reduced by the same percentage. In addition, a significant 44.8% reduction in the cumulative number of gadolinium-enhancing lesions was observed in patients treated with the investigational dosing regimen. At 12 months, there was no significant difference in percentage change of brain volume between the glatiramer acetate-treated patients and those receiving placebo. Discontinuation rates among the two cohorts were comparable.

Glatiramer acetate in a dose of 40 mg/mL also showed a favorable safety and tolerability profile. The overall frequency of adverse events in the GALA study was comparable to that of the placebo group. The most common reported adverse events were injection-site reactions, headaches, and nasopharyngitis.

The drug maker released only top-line data at a press conference. Lead study author Omar A. Khan, MD, Professor and Interim Chair of the Department of Neurology and Director of the Multiple Sclerosis Clinical Research Center and Image Analysis Laboratory at Wayne State University School of Medicine in Detroit, reported more detailed study results two days later on October 13 in a late-breaking news session of the 28th Congress of the ECTRIMS.

Second Phase III Study of Teriflunomide Confirms Significant Impact on Disability
Once-daily oral teriflunomide 14 mg significantly reduced the annualized relapse rate and slowed progression of disability in patients with relapsing forms of multiple sclerosis (MS) compared with placebo, according to data presented at the 28th Congress of ECTRIMS. In addition, the proportion of patients treated with teriflunomide who were relapse-free was significantly higher compared with placebo. 

Ludwig Kappos, MD, Chair of Neurology, University Hospital Basel, Switzerland, and colleagues presented the results of TOWER (Teriflunomide Oral in people With relapsing multiplE scleRosis), the second phase III randomized, double-blind trial of teriflunomide. “The TOWER study results are consistent with the phase III TEMSO data, both in terms of the effect on progression of disability and the manageable safety profile of teriflunomide,”

said Dr. Kappos.

TOWER enrolled 1,169 patients with relapsing-remitting MS across 26 countries and compared 7 mg or 14 mg once-daily oral teriflunomide with placebo.

Dr. Kappos reported that patients treated with 14 mg had a 36.3% reduction in annualized relapse rate (ARR) compared with placebo and 31.5% reduced risk of 12-week sustained disability progression, as measured by the Expanded Disability Status Scale, compared with placebo. Patients treated with 7 mg had a 22.3% reduction in ARR; there was no significant effect of 7 mg on disability progression.

Patients who completed the trial were followed for between 48 and 173 weeks. The average duration of teriflunomide exposure in TOWER was 18 months.

Adverse events observed in the trial were consistent with those seen in previous studies of teriflunomide in MS.

The proportion of patients with treatment-emergent adverse events was similar across all treatment arms. The most common adverse events reported more frequently in the treatment arms were headache, ALT (alanine aminotransferase) elevations, hair thinning, diarrhea, nausea, and neutropenia. As previously reported, there was one death from a respiratory infection in the placebo arm and three deaths in the teriflunomide arms. The three deaths in the treatment arms were attributed to a motor vehicle accident, a suicide, and sepsis.

Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis required for proliferation of rapidly dividing lymphocytes. Teriflunomide thus limits expansion of stimulated T- and B-cells thought responsible for the damaging inflammatory process associated with MS while preserving resting lymphocytes’ function for immune surveillance. Teriflunomide is marketed by Genzyme under the brand name Aubagio. The drug was approved by the FDA on September 12, 2012 as a once-daily, oral immunomodulator indicated for patients with relapsing forms of MS.

Long-Term Safety and Efficacy Data Released for Oral Fingolimod
Four-year data from the phase III FREEDOMS extension study highlight the sustained efficacy of oral fingolimod and reinforce the known safety profile.

At the 28th Congress of ECTRIMS, Ludwig Kappos, MD, and his colleagues presented postmarketing data on the efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (MS) receiving continuous or placebo-fingolimod switched therapy for as many as four years.

Dr. Kappos and colleagues reported that after switching from placebo to fingolimod in the FREEDOMS study extension, patients showed improvements in clinical and MRI outcomes, consistent with the effects observed in fingolimod-treated patients in the core study.

In addition, patients receiving continuous fingolimod treatment during the FREEDOMS core study and extension phase demonstrated sustained, low-disease activity on clinical and MRI end points in the extension phase. These patients also had better overall outcomes than patients switched from placebo to fingolimod.

In continuously treated patients, Dr. Kappos reported, the brain-volume loss benefits observed in the phase III FREEDOMS study were sustained during the extension phase, indicating a long-term effect of fingolimod for as many as four years. In patients switched from placebo to fingolimod, brain-loss benefits were observed early during the first year of active treatment.

Brain-volume loss outcomes were better in continuously treated patients than in switch patients, indicating a smaller overall loss in brain volume with earlier initiation of fingolimod treatment. The percentage of patients free of three-month confirmed disability progression at the end of the study was 74.2% in the continuous 1.25-mg dosage group, 73.9% in the continuous 0.5-mg dosage group, and 66.3% in the placebo-fingolimod switched group.

The percentage of patients free of six-month confirmed disability progression at the end of the study was 79.3% in the continuous 1.25-mg dosage group, 80% in the continuous 0.5-mg dosage group, and 72.7% in the placebo-fingolimod switched group.

Annualized relapse rates at the end of the study were 0.164 in the continuous 1.25-mg dosage group, 0.185 in the continuous 0.5-mg dosage group, and 0.357 in the placebo-fingolimod switched group.

Mean percentage of brain-volume change at the end of the study was -1.6 in the continuous 1.25-mg dosage group, -1.7 in the continuous 0.5-mg dosage group, and -2.2 in the placebo-fingolimod switched group.

LYON, FRANCE—The following news stories were originally written on site at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and posted on the Neurology Reviews website www.neurologyreviews.com. We have reproduced them here for readers who did not see our online conference reporting. More news from the ECTRIMS Congress can be found online and in upcoming issues of Neurology Reviews.

Postmarketing Safety Data Released for Ampyra (Dalfampridine)
Michele Jara, DSc, Director of Epidemiology at Accorda Therapeutics in Hawthorne, New Jersey, and colleagues presented the findings from a two-year safety study of Ampyra (dalfampridine) extended-release tablets (10 mg) indicated for the treatment of walking impairment in patients with multiple sclerosis (MS). Among the major findings, Dr. Jara reported that:

• The safety profile for Ampyra two years after FDA approval is similar to that observed in clinical trials.
• The most frequent associated adverse events were dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, back pain, and asthenia.
• Among the 62,400 patients prescribed Ampyra, the rate of seizure (4.6 per 1,000 patient-years of use) was comparable to that seen in the MS population overall. Length of treatment prior to seizure ranged from first dose to two years, with 20% of the seizures occurring within a week of starting treatment.

The analysis examined all postmarketing data that were reported to the drug maker (Acorda) and the FDA from March 2010 through March 2012.

Teva Announces Top-Line Data From the GALA Study—New Dosing Regimen for Glatiramer Acetate
Data from a phase III trial support the efficacy of a new dosing regimen for Copaxone (glatiramer acetate) for patients with relapsing-remitting multiple sclerosis (MS).

Teva Pharmaceutical Industries released data from the Glatiramer Acetate Low-Frequency Administration (GALA) study, which was designed to evaluate the efficacy, safety, and tolerability of 40 mg/mL of glatiramer acetate three times weekly instead of the 20-mg/mL daily subcutaneous injection that has been the recommended dose for almost two decades.

In the GALA study, a one-year, randomized, double-blind, placebo-controlled trial, glatiramer acetate 40 mg/mL injected three times weekly significantly reduced annualized relapse rates by 34.4% versus placebo. The cumulative number of new and enlarging T2 lesions was significantly reduced by the same percentage. In addition, a significant 44.8% reduction in the cumulative number of gadolinium-enhancing lesions was observed in patients treated with the investigational dosing regimen. At 12 months, there was no significant difference in percentage change of brain volume between the glatiramer acetate-treated patients and those receiving placebo. Discontinuation rates among the two cohorts were comparable.

Glatiramer acetate in a dose of 40 mg/mL also showed a favorable safety and tolerability profile. The overall frequency of adverse events in the GALA study was comparable to that of the placebo group. The most common reported adverse events were injection-site reactions, headaches, and nasopharyngitis.

The drug maker released only top-line data at a press conference. Lead study author Omar A. Khan, MD, Professor and Interim Chair of the Department of Neurology and Director of the Multiple Sclerosis Clinical Research Center and Image Analysis Laboratory at Wayne State University School of Medicine in Detroit, reported more detailed study results two days later on October 13 in a late-breaking news session of the 28th Congress of the ECTRIMS.

Second Phase III Study of Teriflunomide Confirms Significant Impact on Disability
Once-daily oral teriflunomide 14 mg significantly reduced the annualized relapse rate and slowed progression of disability in patients with relapsing forms of multiple sclerosis (MS) compared with placebo, according to data presented at the 28th Congress of ECTRIMS. In addition, the proportion of patients treated with teriflunomide who were relapse-free was significantly higher compared with placebo. 

Ludwig Kappos, MD, Chair of Neurology, University Hospital Basel, Switzerland, and colleagues presented the results of TOWER (Teriflunomide Oral in people With relapsing multiplE scleRosis), the second phase III randomized, double-blind trial of teriflunomide. “The TOWER study results are consistent with the phase III TEMSO data, both in terms of the effect on progression of disability and the manageable safety profile of teriflunomide,”

said Dr. Kappos.

TOWER enrolled 1,169 patients with relapsing-remitting MS across 26 countries and compared 7 mg or 14 mg once-daily oral teriflunomide with placebo.

Dr. Kappos reported that patients treated with 14 mg had a 36.3% reduction in annualized relapse rate (ARR) compared with placebo and 31.5% reduced risk of 12-week sustained disability progression, as measured by the Expanded Disability Status Scale, compared with placebo. Patients treated with 7 mg had a 22.3% reduction in ARR; there was no significant effect of 7 mg on disability progression.

Patients who completed the trial were followed for between 48 and 173 weeks. The average duration of teriflunomide exposure in TOWER was 18 months.

Adverse events observed in the trial were consistent with those seen in previous studies of teriflunomide in MS.

The proportion of patients with treatment-emergent adverse events was similar across all treatment arms. The most common adverse events reported more frequently in the treatment arms were headache, ALT (alanine aminotransferase) elevations, hair thinning, diarrhea, nausea, and neutropenia. As previously reported, there was one death from a respiratory infection in the placebo arm and three deaths in the teriflunomide arms. The three deaths in the treatment arms were attributed to a motor vehicle accident, a suicide, and sepsis.

Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis required for proliferation of rapidly dividing lymphocytes. Teriflunomide thus limits expansion of stimulated T- and B-cells thought responsible for the damaging inflammatory process associated with MS while preserving resting lymphocytes’ function for immune surveillance. Teriflunomide is marketed by Genzyme under the brand name Aubagio. The drug was approved by the FDA on September 12, 2012 as a once-daily, oral immunomodulator indicated for patients with relapsing forms of MS.

Long-Term Safety and Efficacy Data Released for Oral Fingolimod
Four-year data from the phase III FREEDOMS extension study highlight the sustained efficacy of oral fingolimod and reinforce the known safety profile.

At the 28th Congress of ECTRIMS, Ludwig Kappos, MD, and his colleagues presented postmarketing data on the efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (MS) receiving continuous or placebo-fingolimod switched therapy for as many as four years.

Dr. Kappos and colleagues reported that after switching from placebo to fingolimod in the FREEDOMS study extension, patients showed improvements in clinical and MRI outcomes, consistent with the effects observed in fingolimod-treated patients in the core study.

In addition, patients receiving continuous fingolimod treatment during the FREEDOMS core study and extension phase demonstrated sustained, low-disease activity on clinical and MRI end points in the extension phase. These patients also had better overall outcomes than patients switched from placebo to fingolimod.

In continuously treated patients, Dr. Kappos reported, the brain-volume loss benefits observed in the phase III FREEDOMS study were sustained during the extension phase, indicating a long-term effect of fingolimod for as many as four years. In patients switched from placebo to fingolimod, brain-loss benefits were observed early during the first year of active treatment.

Brain-volume loss outcomes were better in continuously treated patients than in switch patients, indicating a smaller overall loss in brain volume with earlier initiation of fingolimod treatment. The percentage of patients free of three-month confirmed disability progression at the end of the study was 74.2% in the continuous 1.25-mg dosage group, 73.9% in the continuous 0.5-mg dosage group, and 66.3% in the placebo-fingolimod switched group.

The percentage of patients free of six-month confirmed disability progression at the end of the study was 79.3% in the continuous 1.25-mg dosage group, 80% in the continuous 0.5-mg dosage group, and 72.7% in the placebo-fingolimod switched group.

Annualized relapse rates at the end of the study were 0.164 in the continuous 1.25-mg dosage group, 0.185 in the continuous 0.5-mg dosage group, and 0.357 in the placebo-fingolimod switched group.

Mean percentage of brain-volume change at the end of the study was -1.6 in the continuous 1.25-mg dosage group, -1.7 in the continuous 0.5-mg dosage group, and -2.2 in the placebo-fingolimod switched group.

LYON, FRANCE—The following news stories were originally written on site at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and posted on the Neurology Reviews website www.neurologyreviews.com. We have reproduced them here for readers who did not see our online conference reporting. More news from the ECTRIMS Congress can be found online and in upcoming issues of Neurology Reviews.

Postmarketing Safety Data Released for Ampyra (Dalfampridine)
Michele Jara, DSc, Director of Epidemiology at Accorda Therapeutics in Hawthorne, New Jersey, and colleagues presented the findings from a two-year safety study of Ampyra (dalfampridine) extended-release tablets (10 mg) indicated for the treatment of walking impairment in patients with multiple sclerosis (MS). Among the major findings, Dr. Jara reported that:

• The safety profile for Ampyra two years after FDA approval is similar to that observed in clinical trials.
• The most frequent associated adverse events were dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, back pain, and asthenia.
• Among the 62,400 patients prescribed Ampyra, the rate of seizure (4.6 per 1,000 patient-years of use) was comparable to that seen in the MS population overall. Length of treatment prior to seizure ranged from first dose to two years, with 20% of the seizures occurring within a week of starting treatment.

The analysis examined all postmarketing data that were reported to the drug maker (Acorda) and the FDA from March 2010 through March 2012.

Teva Announces Top-Line Data From the GALA Study—New Dosing Regimen for Glatiramer Acetate
Data from a phase III trial support the efficacy of a new dosing regimen for Copaxone (glatiramer acetate) for patients with relapsing-remitting multiple sclerosis (MS).

Teva Pharmaceutical Industries released data from the Glatiramer Acetate Low-Frequency Administration (GALA) study, which was designed to evaluate the efficacy, safety, and tolerability of 40 mg/mL of glatiramer acetate three times weekly instead of the 20-mg/mL daily subcutaneous injection that has been the recommended dose for almost two decades.

In the GALA study, a one-year, randomized, double-blind, placebo-controlled trial, glatiramer acetate 40 mg/mL injected three times weekly significantly reduced annualized relapse rates by 34.4% versus placebo. The cumulative number of new and enlarging T2 lesions was significantly reduced by the same percentage. In addition, a significant 44.8% reduction in the cumulative number of gadolinium-enhancing lesions was observed in patients treated with the investigational dosing regimen. At 12 months, there was no significant difference in percentage change of brain volume between the glatiramer acetate-treated patients and those receiving placebo. Discontinuation rates among the two cohorts were comparable.

Glatiramer acetate in a dose of 40 mg/mL also showed a favorable safety and tolerability profile. The overall frequency of adverse events in the GALA study was comparable to that of the placebo group. The most common reported adverse events were injection-site reactions, headaches, and nasopharyngitis.

The drug maker released only top-line data at a press conference. Lead study author Omar A. Khan, MD, Professor and Interim Chair of the Department of Neurology and Director of the Multiple Sclerosis Clinical Research Center and Image Analysis Laboratory at Wayne State University School of Medicine in Detroit, reported more detailed study results two days later on October 13 in a late-breaking news session of the 28th Congress of the ECTRIMS.

Second Phase III Study of Teriflunomide Confirms Significant Impact on Disability
Once-daily oral teriflunomide 14 mg significantly reduced the annualized relapse rate and slowed progression of disability in patients with relapsing forms of multiple sclerosis (MS) compared with placebo, according to data presented at the 28th Congress of ECTRIMS. In addition, the proportion of patients treated with teriflunomide who were relapse-free was significantly higher compared with placebo. 

Ludwig Kappos, MD, Chair of Neurology, University Hospital Basel, Switzerland, and colleagues presented the results of TOWER (Teriflunomide Oral in people With relapsing multiplE scleRosis), the second phase III randomized, double-blind trial of teriflunomide. “The TOWER study results are consistent with the phase III TEMSO data, both in terms of the effect on progression of disability and the manageable safety profile of teriflunomide,”

said Dr. Kappos.

TOWER enrolled 1,169 patients with relapsing-remitting MS across 26 countries and compared 7 mg or 14 mg once-daily oral teriflunomide with placebo.

Dr. Kappos reported that patients treated with 14 mg had a 36.3% reduction in annualized relapse rate (ARR) compared with placebo and 31.5% reduced risk of 12-week sustained disability progression, as measured by the Expanded Disability Status Scale, compared with placebo. Patients treated with 7 mg had a 22.3% reduction in ARR; there was no significant effect of 7 mg on disability progression.

Patients who completed the trial were followed for between 48 and 173 weeks. The average duration of teriflunomide exposure in TOWER was 18 months.

Adverse events observed in the trial were consistent with those seen in previous studies of teriflunomide in MS.

The proportion of patients with treatment-emergent adverse events was similar across all treatment arms. The most common adverse events reported more frequently in the treatment arms were headache, ALT (alanine aminotransferase) elevations, hair thinning, diarrhea, nausea, and neutropenia. As previously reported, there was one death from a respiratory infection in the placebo arm and three deaths in the teriflunomide arms. The three deaths in the treatment arms were attributed to a motor vehicle accident, a suicide, and sepsis.

Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis required for proliferation of rapidly dividing lymphocytes. Teriflunomide thus limits expansion of stimulated T- and B-cells thought responsible for the damaging inflammatory process associated with MS while preserving resting lymphocytes’ function for immune surveillance. Teriflunomide is marketed by Genzyme under the brand name Aubagio. The drug was approved by the FDA on September 12, 2012 as a once-daily, oral immunomodulator indicated for patients with relapsing forms of MS.

Long-Term Safety and Efficacy Data Released for Oral Fingolimod
Four-year data from the phase III FREEDOMS extension study highlight the sustained efficacy of oral fingolimod and reinforce the known safety profile.

At the 28th Congress of ECTRIMS, Ludwig Kappos, MD, and his colleagues presented postmarketing data on the efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (MS) receiving continuous or placebo-fingolimod switched therapy for as many as four years.

Dr. Kappos and colleagues reported that after switching from placebo to fingolimod in the FREEDOMS study extension, patients showed improvements in clinical and MRI outcomes, consistent with the effects observed in fingolimod-treated patients in the core study.

In addition, patients receiving continuous fingolimod treatment during the FREEDOMS core study and extension phase demonstrated sustained, low-disease activity on clinical and MRI end points in the extension phase. These patients also had better overall outcomes than patients switched from placebo to fingolimod.

In continuously treated patients, Dr. Kappos reported, the brain-volume loss benefits observed in the phase III FREEDOMS study were sustained during the extension phase, indicating a long-term effect of fingolimod for as many as four years. In patients switched from placebo to fingolimod, brain-loss benefits were observed early during the first year of active treatment.

Brain-volume loss outcomes were better in continuously treated patients than in switch patients, indicating a smaller overall loss in brain volume with earlier initiation of fingolimod treatment. The percentage of patients free of three-month confirmed disability progression at the end of the study was 74.2% in the continuous 1.25-mg dosage group, 73.9% in the continuous 0.5-mg dosage group, and 66.3% in the placebo-fingolimod switched group.

The percentage of patients free of six-month confirmed disability progression at the end of the study was 79.3% in the continuous 1.25-mg dosage group, 80% in the continuous 0.5-mg dosage group, and 72.7% in the placebo-fingolimod switched group.

Annualized relapse rates at the end of the study were 0.164 in the continuous 1.25-mg dosage group, 0.185 in the continuous 0.5-mg dosage group, and 0.357 in the placebo-fingolimod switched group.

Mean percentage of brain-volume change at the end of the study was -1.6 in the continuous 1.25-mg dosage group, -1.7 in the continuous 0.5-mg dosage group, and -2.2 in the placebo-fingolimod switched group.