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LONDON—Opicinumab, an investigational remyelinating agent, may promote clinical improvement in patients with multiple sclerosis (MS) who are receiving interferon beta-1a, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. The monoclonal antibody appears not to have a linear dose response; the high and low doses are associated with less improvement than the moderate doses.
In a phase IIb study, patients with relapsing-remitting MS, shorter disease duration, and less severe damage to the brain had a stronger response to opicinumab. “These biological markers are, we believe, valuable to inform all future steps,” said Diego Cadavid, MD, Senior Director at Biogen in Cambridge, Massachusetts. Opicinumab was generally well tolerated. The main adverse events were hypersensitivity reactions that occurred at a dose of 100 mg/kg. 
Testing Effects on Pre-Existing Disability
Dr. Cadavid and colleagues conducted the SYNERGY trial to assess the efficacy of four doses of opicinumab versus placebo in patients with MS, pre-existing disability, and recent active relapse. Of the 418 patients enrolled, 80% had relapsing-remitting MS and 20% had secondary progressive MS. All participants were receiving intramuscular interferon beta-1a.
The investigators randomized patients to placebo or one of four doses of opicinumab (ie, 3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg). A total of 418 participants were randomized and dosed; 334 completed the study. The treatment period was 72 weeks, and a final safety and efficacy analysis occurred at 84 weeks. The primary end point was confirmed improvement on Expanded Disability Status Scale (EDSS) score, Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), or 3-second Paced Auditory Serial Addition Test (PASAT-3).
The majority of participants were female, and mean age at baseline was approximately 40. Average disease duration was approximately 10 years. The median EDSS score was 3.5. Mean T25FW score was approximately 8 seconds. Mean 9HPT score was 25 seconds. Mean PASAT-3 score was 49. Randomization resulted in well-balanced treatment groups.
Moderate Doses Brought Most Benefit
Increasing doses of opicinumab did not lead to increases in the percentage of patients experiencing improvement of pre-existing disability. The estimated percentage of improvement responders was 52% for placebo, 51% for the 3-mg/kg dose, 66% for the 10-mg/kg dose, 69% for the 30-mg/kg dose, and 41% for the 100-mg/kg dose.
“We have observed an inverted-U dose response for the improvement of pre-existing disability with opicinumab,” said Dr. Cadavid. The odds ratios for improvement on the EDSS and the 9HPT were greatest for the 10-mg/kg dose. The odds ratio for improvement on the T25FW was greatest for the 3-mg dose. The odds ratio for improvement on PASAT-3 was greatest for the 30-mg/kg dose. The study, however, was not powered for any individual component.
Participants with better whole brain multispectral thermal imaging, greater whole brain radial diffusivity on diffusion tensor imaging (DTI RD), and greater normalized whole brain volume responded better to opicinumab. The strongest odds ratios in this univariable analysis were observed on the DTI RD at 10 mg/kg.
“Further work is clearly needed to understand what explains the behavior of opicinumab at the highest dose,” said Dr. Cadavid. “We have identified an appropriate patient population, a dose and exposure, and end points to inform the next study, and [we] are in the process of evaluating the optimized study design.”
—Erik Greb
LONDON—Opicinumab, an investigational remyelinating agent, may promote clinical improvement in patients with multiple sclerosis (MS) who are receiving interferon beta-1a, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. The monoclonal antibody appears not to have a linear dose response; the high and low doses are associated with less improvement than the moderate doses.
In a phase IIb study, patients with relapsing-remitting MS, shorter disease duration, and less severe damage to the brain had a stronger response to opicinumab. “These biological markers are, we believe, valuable to inform all future steps,” said Diego Cadavid, MD, Senior Director at Biogen in Cambridge, Massachusetts. Opicinumab was generally well tolerated. The main adverse events were hypersensitivity reactions that occurred at a dose of 100 mg/kg.
Testing Effects on Pre-Existing Disability
Dr. Cadavid and colleagues conducted the SYNERGY trial to assess the efficacy of four doses of opicinumab versus placebo in patients with MS, pre-existing disability, and recent active relapse. Of the 418 patients enrolled, 80% had relapsing-remitting MS and 20% had secondary progressive MS. All participants were receiving intramuscular interferon beta-1a.
The investigators randomized patients to placebo or one of four doses of opicinumab (ie, 3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg). A total of 418 participants were randomized and dosed; 334 completed the study. The treatment period was 72 weeks, and a final safety and efficacy analysis occurred at 84 weeks. The primary end point was confirmed improvement on Expanded Disability Status Scale (EDSS) score, Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), or 3-second Paced Auditory Serial Addition Test (PASAT-3).
The majority of participants were female, and mean age at baseline was approximately 40. Average disease duration was approximately 10 years. The median EDSS score was 3.5. Mean T25FW score was approximately 8 seconds. Mean 9HPT score was 25 seconds. Mean PASAT-3 score was 49. Randomization resulted in well-balanced treatment groups.
Moderate Doses Brought Most Benefit
Increasing doses of opicinumab did not lead to increases in the percentage of patients experiencing improvement of pre-existing disability. The estimated percentage of improvement responders was 52% for placebo, 51% for the 3-mg/kg dose, 66% for the 10-mg/kg dose, 69% for the 30-mg/kg dose, and 41% for the 100-mg/kg dose.
“We have observed an inverted-U dose response for the improvement of pre-existing disability with opicinumab,” said Dr. Cadavid. The odds ratios for improvement on the EDSS and the 9HPT were greatest for the 10-mg/kg dose. The odds ratio for improvement on the T25FW was greatest for the 3-mg dose. The odds ratio for improvement on PASAT-3 was greatest for the 30-mg/kg dose. The study, however, was not powered for any individual component.
Participants with better whole brain multispectral thermal imaging, greater whole brain radial diffusivity on diffusion tensor imaging (DTI RD), and greater normalized whole brain volume responded better to opicinumab. The strongest odds ratios in this univariable analysis were observed on the DTI RD at 10 mg/kg.
“Further work is clearly needed to understand what explains the behavior of opicinumab at the highest dose,” said Dr. Cadavid. “We have identified an appropriate patient population, a dose and exposure, and end points to inform the next study, and [we] are in the process of evaluating the optimized study design.”
—Erik Greb
LONDON—Opicinumab, an investigational remyelinating agent, may promote clinical improvement in patients with multiple sclerosis (MS) who are receiving interferon beta-1a, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. The monoclonal antibody appears not to have a linear dose response; the high and low doses are associated with less improvement than the moderate doses.
In a phase IIb study, patients with relapsing-remitting MS, shorter disease duration, and less severe damage to the brain had a stronger response to opicinumab. “These biological markers are, we believe, valuable to inform all future steps,” said Diego Cadavid, MD, Senior Director at Biogen in Cambridge, Massachusetts. Opicinumab was generally well tolerated. The main adverse events were hypersensitivity reactions that occurred at a dose of 100 mg/kg.
Testing Effects on Pre-Existing Disability
Dr. Cadavid and colleagues conducted the SYNERGY trial to assess the efficacy of four doses of opicinumab versus placebo in patients with MS, pre-existing disability, and recent active relapse. Of the 418 patients enrolled, 80% had relapsing-remitting MS and 20% had secondary progressive MS. All participants were receiving intramuscular interferon beta-1a.
The investigators randomized patients to placebo or one of four doses of opicinumab (ie, 3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg). A total of 418 participants were randomized and dosed; 334 completed the study. The treatment period was 72 weeks, and a final safety and efficacy analysis occurred at 84 weeks. The primary end point was confirmed improvement on Expanded Disability Status Scale (EDSS) score, Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), or 3-second Paced Auditory Serial Addition Test (PASAT-3).
The majority of participants were female, and mean age at baseline was approximately 40. Average disease duration was approximately 10 years. The median EDSS score was 3.5. Mean T25FW score was approximately 8 seconds. Mean 9HPT score was 25 seconds. Mean PASAT-3 score was 49. Randomization resulted in well-balanced treatment groups.
Moderate Doses Brought Most Benefit
Increasing doses of opicinumab did not lead to increases in the percentage of patients experiencing improvement of pre-existing disability. The estimated percentage of improvement responders was 52% for placebo, 51% for the 3-mg/kg dose, 66% for the 10-mg/kg dose, 69% for the 30-mg/kg dose, and 41% for the 100-mg/kg dose.
“We have observed an inverted-U dose response for the improvement of pre-existing disability with opicinumab,” said Dr. Cadavid. The odds ratios for improvement on the EDSS and the 9HPT were greatest for the 10-mg/kg dose. The odds ratio for improvement on the T25FW was greatest for the 3-mg dose. The odds ratio for improvement on PASAT-3 was greatest for the 30-mg/kg dose. The study, however, was not powered for any individual component.
Participants with better whole brain multispectral thermal imaging, greater whole brain radial diffusivity on diffusion tensor imaging (DTI RD), and greater normalized whole brain volume responded better to opicinumab. The strongest odds ratios in this univariable analysis were observed on the DTI RD at 10 mg/kg.
“Further work is clearly needed to understand what explains the behavior of opicinumab at the highest dose,” said Dr. Cadavid. “We have identified an appropriate patient population, a dose and exposure, and end points to inform the next study, and [we] are in the process of evaluating the optimized study design.”
—Erik Greb
