Daclizumab Reduces MS Relapse Rate by 45%, Compared With Interferon β-1a

WASHINGTON, DC—Treatment with daclizumab high-yield process (DAC HYP), a first-in-class immunomodulator administered subcutaneously once per month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis (MS) than was interferon (IFN) β-1a therapy, according to results from the international DECIDE study presented at the 67th Annual Meeting of the American Academy of Neurology.

The efficacy of DAC HYP was consistently superior to that of once-weekly intramuscular IFN β-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over the study’s treatment period of 96 to 144 weeks, said Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel and of the DECIDE study’s advisory committee. DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” he said.

Treatment with DAC HYP was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which were “manageable with standard monitoring and medical interventions,” Dr. Kappos said.

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 receptor subunit CD25, which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

Reduction in Relapse Rate Was Highly Significant
The DECIDE phase III study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every four weeks and 922 patients to treatment with 30 mg of IFN β-1a administered intramuscularly once per week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of five years. Patients in both groups had had a similar mean number of relapses within the previous year (between 0.7 and 0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously. Their mean Expanded Disability Status Scale (EDSS) score was between 1.2 and 1.3. In both arms, approximately 30% of patients discontinued treatment. The percentage of patients that discontinued treatment because of adverse events was higher in the DAC HYP-treated group.

The annualized relapse rate—the study’s primary end point—was 0.393 among those on IFN β-1a, compared with 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant, Dr. Kappos said.

Secondary end points included the proportion of patients who remained relapse-free, which was higher among those on DAC HYP at various points during the study (eg, 73% vs 59% at week 96, and 67% vs 51% at week 144). The risk of relapse was reduced by 41%.

Other secondary end points were MRI-defined lesions at week 96. The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN β-1a. There were similar reductions in new T1 black holes, which were reduced by 52%, and in gadolinium-enhancing lesions, which were reduced by 65%. There was a significant positive effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At three months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN β-1a, although the effect was not statistically significant. At six months, the risk was reduced by 27%. The proportion of patients on DAC HYP with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5-point decrease on MSIS-29-PHYS) was reduced by 24%, compared with those on IFN β-1a. The reduction was not statistically significant.

Hepatic Abnormalities Were More Common in Daclizumab Patients
The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs 21%); when MS relapses were excluded, the rates were 15% and 10%. Treatment discontinuations due to an adverse event other than an MS relapse were 14% among those on DAC HYP, compared with 9% of those on IFN β-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs 57%), as was the rate of serious infectious adverse events (4% vs 2%). Cutaneous events were more common among those on DAC HYP (37% vs 19%), as were serious cutaneous adverse events (2% vs less than 1%).

Hepatic abnormalities were more common among those on DAC HYP, but were reversible, Dr. Kappos said. The rate of aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than five times the upper limit of normal (ULN) was 6% among those on DAC HYP, compared with 3% among those on IFN β-1a. The rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case in each group that met Hy’s law criteria, which are used to predict the potential of drugs to cause serious liver injury.

Biogen Idec and AbbVie Biotherapeutics funded the study.

—Elizabeth Mechcatie

WASHINGTON, DC—Treatment with daclizumab high-yield process (DAC HYP), a first-in-class immunomodulator administered subcutaneously once per month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis (MS) than was interferon (IFN) β-1a therapy, according to results from the international DECIDE study presented at the 67th Annual Meeting of the American Academy of Neurology.

The efficacy of DAC HYP was consistently superior to that of once-weekly intramuscular IFN β-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over the study’s treatment period of 96 to 144 weeks, said Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel and of the DECIDE study’s advisory committee. DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” he said.

Treatment with DAC HYP was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which were “manageable with standard monitoring and medical interventions,” Dr. Kappos said.

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 receptor subunit CD25, which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

Reduction in Relapse Rate Was Highly Significant
The DECIDE phase III study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every four weeks and 922 patients to treatment with 30 mg of IFN β-1a administered intramuscularly once per week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of five years. Patients in both groups had had a similar mean number of relapses within the previous year (between 0.7 and 0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously. Their mean Expanded Disability Status Scale (EDSS) score was between 1.2 and 1.3. In both arms, approximately 30% of patients discontinued treatment. The percentage of patients that discontinued treatment because of adverse events was higher in the DAC HYP-treated group.

The annualized relapse rate—the study’s primary end point—was 0.393 among those on IFN β-1a, compared with 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant, Dr. Kappos said.

Secondary end points included the proportion of patients who remained relapse-free, which was higher among those on DAC HYP at various points during the study (eg, 73% vs 59% at week 96, and 67% vs 51% at week 144). The risk of relapse was reduced by 41%.

Other secondary end points were MRI-defined lesions at week 96. The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN β-1a. There were similar reductions in new T1 black holes, which were reduced by 52%, and in gadolinium-enhancing lesions, which were reduced by 65%. There was a significant positive effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At three months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN β-1a, although the effect was not statistically significant. At six months, the risk was reduced by 27%. The proportion of patients on DAC HYP with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5-point decrease on MSIS-29-PHYS) was reduced by 24%, compared with those on IFN β-1a. The reduction was not statistically significant.

Hepatic Abnormalities Were More Common in Daclizumab Patients
The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs 21%); when MS relapses were excluded, the rates were 15% and 10%. Treatment discontinuations due to an adverse event other than an MS relapse were 14% among those on DAC HYP, compared with 9% of those on IFN β-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs 57%), as was the rate of serious infectious adverse events (4% vs 2%). Cutaneous events were more common among those on DAC HYP (37% vs 19%), as were serious cutaneous adverse events (2% vs less than 1%).

Hepatic abnormalities were more common among those on DAC HYP, but were reversible, Dr. Kappos said. The rate of aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than five times the upper limit of normal (ULN) was 6% among those on DAC HYP, compared with 3% among those on IFN β-1a. The rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case in each group that met Hy’s law criteria, which are used to predict the potential of drugs to cause serious liver injury.

Biogen Idec and AbbVie Biotherapeutics funded the study.

—Elizabeth Mechcatie

WASHINGTON, DC—Treatment with daclizumab high-yield process (DAC HYP), a first-in-class immunomodulator administered subcutaneously once per month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis (MS) than was interferon (IFN) β-1a therapy, according to results from the international DECIDE study presented at the 67th Annual Meeting of the American Academy of Neurology.

The efficacy of DAC HYP was consistently superior to that of once-weekly intramuscular IFN β-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over the study’s treatment period of 96 to 144 weeks, said Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel and of the DECIDE study’s advisory committee. DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” he said.

Treatment with DAC HYP was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which were “manageable with standard monitoring and medical interventions,” Dr. Kappos said.

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 receptor subunit CD25, which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

Reduction in Relapse Rate Was Highly Significant
The DECIDE phase III study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every four weeks and 922 patients to treatment with 30 mg of IFN β-1a administered intramuscularly once per week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of five years. Patients in both groups had had a similar mean number of relapses within the previous year (between 0.7 and 0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously. Their mean Expanded Disability Status Scale (EDSS) score was between 1.2 and 1.3. In both arms, approximately 30% of patients discontinued treatment. The percentage of patients that discontinued treatment because of adverse events was higher in the DAC HYP-treated group.

The annualized relapse rate—the study’s primary end point—was 0.393 among those on IFN β-1a, compared with 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant, Dr. Kappos said.

Secondary end points included the proportion of patients who remained relapse-free, which was higher among those on DAC HYP at various points during the study (eg, 73% vs 59% at week 96, and 67% vs 51% at week 144). The risk of relapse was reduced by 41%.

Other secondary end points were MRI-defined lesions at week 96. The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN β-1a. There were similar reductions in new T1 black holes, which were reduced by 52%, and in gadolinium-enhancing lesions, which were reduced by 65%. There was a significant positive effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At three months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN β-1a, although the effect was not statistically significant. At six months, the risk was reduced by 27%. The proportion of patients on DAC HYP with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5-point decrease on MSIS-29-PHYS) was reduced by 24%, compared with those on IFN β-1a. The reduction was not statistically significant.

Hepatic Abnormalities Were More Common in Daclizumab Patients
The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs 21%); when MS relapses were excluded, the rates were 15% and 10%. Treatment discontinuations due to an adverse event other than an MS relapse were 14% among those on DAC HYP, compared with 9% of those on IFN β-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs 57%), as was the rate of serious infectious adverse events (4% vs 2%). Cutaneous events were more common among those on DAC HYP (37% vs 19%), as were serious cutaneous adverse events (2% vs less than 1%).

Hepatic abnormalities were more common among those on DAC HYP, but were reversible, Dr. Kappos said. The rate of aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than five times the upper limit of normal (ULN) was 6% among those on DAC HYP, compared with 3% among those on IFN β-1a. The rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case in each group that met Hy’s law criteria, which are used to predict the potential of drugs to cause serious liver injury.

Biogen Idec and AbbVie Biotherapeutics funded the study.

—Elizabeth Mechcatie