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What is opicinumab (anti-LINGO-1)?
Opicinumab
(anti-LINGO-1) is an investigational compound being developed as a potential
neuroreparative therapy for the treatment of multiple sclerosis (MS). In MS, the immune system attacks the myelin
(fatty substance that surrounds and protects the nerve fibers) in the central
nervous system (CNS), causing damage or destruction. This process is called “demyelination.” As the damage progresses, nerve cells may
eventually die, likely contributing to physical and cognitive disability.[1]
(anti-LINGO-1) is an investigational compound being developed as a potential
neuroreparative therapy for the treatment of multiple sclerosis (MS). In MS, the immune system attacks the myelin
(fatty substance that surrounds and protects the nerve fibers) in the central
nervous system (CNS), causing damage or destruction. This process is called “demyelination.” As the damage progresses, nerve cells may
eventually die, likely contributing to physical and cognitive disability.[1]
Opicinumab
(anti-LINGO-1) is being studied for its potential to regenerate the protective
sheath around nerves (remyelination), which may help protect against additional
cell damage and may restore some nerve cell function.
(anti-LINGO-1) is being studied for its potential to regenerate the protective
sheath around nerves (remyelination), which may help protect against additional
cell damage and may restore some nerve cell function.
Biogen hypothesizes that a neuroreparative therapy may repair
damage caused by MS, which could result in improved neurologic function.
damage caused by MS, which could result in improved neurologic function.
What is the difference between opicinumab
(anti-LINGO-1) and existing MS disease-modifying therapies (DMTs)?
(anti-LINGO-1) and existing MS disease-modifying therapies (DMTs)?
Existing DMTs
control inflammation by modulating or suppressing the immune system and
potentially impacting the course of the disease (e.g., reduction of relapses or
slowing worsening of disability).
control inflammation by modulating or suppressing the immune system and
potentially impacting the course of the disease (e.g., reduction of relapses or
slowing worsening of disability).
Opicinumab (anti-LINGO-1) does not control
inflammation; it is being studied for its potential to regenerate the
protective sheath around nerves (remyelination), which may help restore some
nerve cell function.
inflammation; it is being studied for its potential to regenerate the
protective sheath around nerves (remyelination), which may help restore some
nerve cell function.
What is the SYNERGY study?
SYNERGY is a randomized, double-blind, placebo-controlled,
dose-ranging Phase 2 study that evaluated the impact of opicinumab (anti-LINGO-1) among 418 participants with relapsing forms of MS (RMS), both relapsing-remitting
and secondary progressive, over 72 weeks. All study participants
received concurrent treatment with 30 mcg interferon beta-1a intramuscular (IM)
injections once weekly.
dose-ranging Phase 2 study that evaluated the impact of opicinumab (anti-LINGO-1) among 418 participants with relapsing forms of MS (RMS), both relapsing-remitting
and secondary progressive, over 72 weeks. All study participants
received concurrent treatment with 30 mcg interferon beta-1a intramuscular (IM)
injections once weekly.
The primary objective of the SYNERGY study was to evaluate the efficacy
of opicinumab (anti-LINGO-1) in participants with active RMS when used
concurrently with interferon beta-1a IM. The primary endpoint
was the percentage of participants who experienced improvement relative to
placebo on one or more of the following multicomponent measures: ambulation (Timed 25-Foot Walk; T25FW); upper
extremity function (9-Hole Peg Test; 9HPT); cognition (3-Second
Paced Auditory Serial Addition Test; PASAT); and a standard measure of physical disability (Expanded
Disability Status Scale; EDSS).
of opicinumab (anti-LINGO-1) in participants with active RMS when used
concurrently with interferon beta-1a IM. The primary endpoint
was the percentage of participants who experienced improvement relative to
placebo on one or more of the following multicomponent measures: ambulation (Timed 25-Foot Walk; T25FW); upper
extremity function (9-Hole Peg Test; 9HPT); cognition (3-Second
Paced Auditory Serial Addition Test; PASAT); and a standard measure of physical disability (Expanded
Disability Status Scale; EDSS).
The secondary efficacy endpoint was the percentage of participants who experienced worsening on the same multicomponent measures relative to placebo. Other secondary objectives of the study were the safety and pharmacokinetics of
opicinumab (anti-LINGO-1).
opicinumab (anti-LINGO-1).
SYNERGY was the first Phase 2 MS study that evaluated
improvement in clinical outcomes in participants being treated with a potential
remyelinating agent.
improvement in clinical outcomes in participants being treated with a potential
remyelinating agent.
[1] Chari DM. Remyelination in multiple sclerosis. Int Rev Neurobiol. 2007;79:589-620.
What does
“double-blind” mean?
“double-blind” mean?
“Double-blind”
means that none of the participants, their care partners, the companies sponsoring
the study, nor the study staff will know if the participant is/was assigned to
the drug or placebo group while the study is ongoing.
means that none of the participants, their care partners, the companies sponsoring
the study, nor the study staff will know if the participant is/was assigned to
the drug or placebo group while the study is ongoing.
What does “randomized, placebo-controlled, dose-ranging”
mean?
mean?
A randomized and
placebo-controlled study means
everyone participating in the study was randomly assigned to receive interferon
beta-1a IM and either placebo or one of four doses of opicinumab (anti-LINGO-1):
3 mg/kg; 10 mg/kg; 30 mg/kg; or 100 mg/kg. A study with multiple doses is known as a
“dose-ranging” study and is usually performed in the early stages of drug
development to provide more information for future studies.
placebo-controlled study means
everyone participating in the study was randomly assigned to receive interferon
beta-1a IM and either placebo or one of four doses of opicinumab (anti-LINGO-1):
3 mg/kg; 10 mg/kg; 30 mg/kg; or 100 mg/kg. A study with multiple doses is known as a
“dose-ranging” study and is usually performed in the early stages of drug
development to provide more information for future studies.
How is opicinumab (anti-LINGO-1)
administered?
administered?
In the SYNERGY study, opicinumab (anti-LINGO-1) was administered as an intravenous infusion every four weeks at doses of 3 mg/kg, 10 mg/kg, 30 mg/kg or 100 mg/kg. All study participants
received concurrent treatment with 30 mcg interferon beta-1a IM injections once weekly.
received concurrent treatment with 30 mcg interferon beta-1a IM injections once weekly.
What are the results
of SYNERGY?
of SYNERGY?
In the study, opicinumab (anti-LINGO-1) missed the
primary endpoint which was a multicomponent measure evaluating improvement of
physical function, cognitive function, and disability relative to placebo. However,
evidence of a clinical effect with a complex, unexpected dose-response was
observed. Biogen is planning to have additional information available at
ECTRIMS in September if accepted.
primary endpoint which was a multicomponent measure evaluating improvement of
physical function, cognitive function, and disability relative to placebo. However,
evidence of a clinical effect with a complex, unexpected dose-response was
observed. Biogen is planning to have additional information available at
ECTRIMS in September if accepted.
Opicinumab also did not meet the secondary endpoint,
which evaluated the slowing of disability progression. All study participants
received concurrent treatment with 30 mcg interferon beta-1a intramuscular
injection (IM) once weekly.
which evaluated the slowing of disability progression. All study participants
received concurrent treatment with 30 mcg interferon beta-1a intramuscular
injection (IM) once weekly.
The SYNERGY results
provide a rich data set that will advance our understanding of the potential to
repair damage in the CNS caused by MS or other demyelinating diseases. Biogen is continuing to analyze large amounts
of data from this comprehensive Phase 2 study to inform potential next steps.
provide a rich data set that will advance our understanding of the potential to
repair damage in the CNS caused by MS or other demyelinating diseases. Biogen is continuing to analyze large amounts
of data from this comprehensive Phase 2 study to inform potential next steps.
What were the side
effects of opicinumab (anti-LINGO-1) seen in the SYNERGY trial?
effects of opicinumab (anti-LINGO-1) seen in the SYNERGY trial?
Opicinumab was
generally well-tolerated and the safety profile was consistent with what has
been observed in prior studies.
generally well-tolerated and the safety profile was consistent with what has
been observed in prior studies.
What are the next steps? Will there be
another study?
another study?
SYNERGY was a comprehensive
Phase 2 study of 418 participants, so there are large amounts of data to be
analyzed, including additional endpoints. Biogen continues to analyze the data to inform
the next step of the clinical development program, including the design of a
next study. Biogen plans to present additional SYNERGY results at ECTRIMS if
accepted.
Phase 2 study of 418 participants, so there are large amounts of data to be
analyzed, including additional endpoints. Biogen continues to analyze the data to inform
the next step of the clinical development program, including the design of a
next study. Biogen plans to present additional SYNERGY results at ECTRIMS if
accepted.
Where can I go for
further information about opicinumab (anti-LINGO-1) and/or SYNERGY?
Updates regarding the opicinumab (anti-LINGO-1) clinical trial program will be posted on www.clinicaltrials.gov. You can access this information by searching (anti-LINGO
or NCT01864148). Biogen plans to
present additional SYNERGY study results at ECTRIMS if accepted.
or NCT01864148). Biogen plans to
present additional SYNERGY study results at ECTRIMS if accepted.
We know that Biogen
is conducting other neuroreparative studies. Since the trial results did not
meet expectations, will you continue with the other studies? Will this affect
the trial design of these other studies?
is conducting other neuroreparative studies. Since the trial results did not
meet expectations, will you continue with the other studies? Will this affect
the trial design of these other studies?
Biogen is evaluating the data and
will assess any potential impact of SYNERGY on future studies. The SYNERGY
results provide a rich data set that will advance our understanding around the
potential to repair damage in the CNS caused by MS and other demyelinating
diseases. Biogen intends to use the findings
from this study and other data as neuroreparative research efforts are
continued.
will assess any potential impact of SYNERGY on future studies. The SYNERGY
results provide a rich data set that will advance our understanding around the
potential to repair damage in the CNS caused by MS and other demyelinating
diseases. Biogen intends to use the findings
from this study and other data as neuroreparative research efforts are
continued.
Once Biogen completes a thorough
review of the SYNERGY data, Biogen will make and communicate an informed
decision about next steps.
review of the SYNERGY data, Biogen will make and communicate an informed
decision about next steps.
###
[1] Chari DM.
Remyelination in multiple sclerosis. Int Rev Neurobiol. 2007;79:589-620.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17531860. Accessed May 24, 2016.
Remyelination in multiple sclerosis. Int Rev Neurobiol. 2007;79:589-620.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17531860. Accessed May 24, 2016.
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