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Last updated: 12 Apr 2016

BIIB033

Summary
Trade name: 
Opicinumab
(16)
Biogen Data at 2016 AAN Annual Meeting Highlight Its Expansive Portfolio of MS Therapies That Meets Diverse Needs of Patients
Biogen, 12 Apr 2016
Accessed on 12 Apr 2016 from http://media.biogen.com/press-release/corporate/biogen-data-2016-aan-annual-meeting-highlight-its-expansive-portfolio-ms-the.
Class: 
Neuroprotector
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
Target: 
LINGO-1 ("leucine-rich repeat and immunoglobulin-like domain–containing, Nogo receptor–interacting protein")
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
(2)
LINGO-1 negatively regulates myelination by oligodendrocytes.
Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G, Levesque M, Zhang M, et al.
Nat Neurosci. 2005 Jun; 8(6):745-51. Epub 2005 May 15. PMID: 15895088. Abstract
Status for MS: 
Phase I results have been published
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Phase II trial is recruiting as of May, 2014
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Administration: 
Intravenous infusion used in Phase I and Phase II trials
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Subcutaneous injection used in Phase I trial
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Commercial: 
Discovered by Biogen Idec
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
Clinical trials are sponsored by Biogen Idec
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
Biogen Idec, which is developing BIIB033, has changed its name to Biogen (23 March 2015)
(15)
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
Names
Name: 
BIIB033
Trade name: 
Opicinumab
(16)
Biogen Data at 2016 AAN Annual Meeting Highlight Its Expansive Portfolio of MS Therapies That Meets Diverse Needs of Patients
Biogen, 12 Apr 2016
Accessed on 12 Apr 2016 from http://media.biogen.com/press-release/corporate/biogen-data-2016-aan-annual-meeting-highlight-its-expansive-portfolio-ms-the.
Synonyms: 
Anti-LINGO-1 antibody
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
Anti-LINGO-1 mAb
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
Li81
(7)
Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.
Pepinsky R B, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S
J Pharmacol Exp Ther. 2014 Apr 22. PMID: 24756303. Abstract
Physiology
Class: 
Neuroprotector
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
Target: 
LINGO-1 ("leucine-rich repeat and immunoglobulin-like domain–containing, Nogo receptor–interacting protein")
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
(2)
LINGO-1 negatively regulates myelination by oligodendrocytes.
Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G, Levesque M, Zhang M, et al.
Nat Neurosci. 2005 Jun; 8(6):745-51. Epub 2005 May 15. PMID: 15895088. Abstract
Properties: 
Human aglycosyl IgG1 monoclonal antibody
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Crystal structure of a complex between the Fab fragment (region of the antibody that binds to antigens) and the extracellular region of human LINGO-1 has been determined
(7)
Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.
Pepinsky R B, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S
J Pharmacol Exp Ther. 2014 Apr 22. PMID: 24756303. Abstract
Serum pharmacokinetics have been determined in both healthy individuals and individuals with MS and are similar in the two groups
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Serum half-life values range from 15 to 24 days after intravenous infusion
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Absorption is slow after subcutaneous injection, but the mean terminal half-life is similar to that after intravenous infusion, about 15 days
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Intravenous doses >3 mg per kg in humans lead to serum concentrations that are predicted to have pharmacological activity, based on remyelination studies in rats
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Cerebrospinal fluid (CSF) pharmacokinetics have been studied; the ratios of CSF to serum concentrations are quite variable between individuals
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Ratio of brain and spinal cord to plasma concentrations is likely to be about 0.1% in humans
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Concentrations in the central nervous system after systemic administration in rats are 0.1 to 0.4% of blood levels
(9)
Exposure levels of anti-LINGO-1 Li81 antibody in the central nervous system and dose-efficacy relationships in rat spinal cord remyelination models after systemic administration.
Pepinsky BR, Shao Z, Ji B, Wang Q, Meng G, Walus L, Lee X, Hu Y, Graff C, Garber E, et al.
J Pharmacol Exp Ther. 2011 Nov; 339(2):519-29. Epub 2011 Aug 01. PMID: 21807883. Abstract

Mechanisms/Effects

Human: 
Binds to a leucine-rich repeat domain of LINGO-1, as shown by structural studies
(7)
Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.
Pepinsky R B, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S
J Pharmacol Exp Ther. 2014 Apr 22. PMID: 24756303. Abstract
Binding of the Fab (fragment antibody-binding) region of the antibody to LINGO-1 blocks contact points in LINGO-1 used in oligomerization
(7)
Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.
Pepinsky R B, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S
J Pharmacol Exp Ther. 2014 Apr 22. PMID: 24756303. Abstract
Binding of the Fab (fragment antibody-binding) region of the antibody to LINGO-1 results in the formation of a stable complex comprised of 2 copies of LINGO-1 and 2 copies of Fab
(7)
Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.
Pepinsky R B, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S
J Pharmacol Exp Ther. 2014 Apr 22. PMID: 24756303. Abstract
Binding of the Fab (fragment antibody-binding) region of the antibody to LINGO-1, and the resulting complex formation, blocks epitopes in the LINGO-1 IgG domain that function in oligodendrocyte differentiation
(7)
Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.
Pepinsky R B, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S
J Pharmacol Exp Ther. 2014 Apr 22. PMID: 24756303. Abstract
Animal: 
Promotes remyelination of the spinal cord in rodent experimental autoimmune encephalomyelitis model, because target molecule (LINGO-1) negatively regulates myelination
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
(2)
LINGO-1 negatively regulates myelination by oligodendrocytes.
Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G, Levesque M, Zhang M, et al.
Nat Neurosci. 2005 Jun; 8(6):745-51. Epub 2005 May 15. PMID: 15895088. Abstract
Promotes differentiation of oligodendrocyte precursor cells and myelination in vitro
(6)
Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells.
Mi S, Miller RH, Tang W, Lee X, Hu B, Wu W, Zhang Y, Shields CB, Zhang Y, Miklasz S, et al.
Ann Neurol. 2009 Mar; 65(3):304-15. PMID: 19334062. Abstract
Accelerates remyelination in vivo in rodent models
(6)
Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells.
Mi S, Miller RH, Tang W, Lee X, Hu B, Wu W, Zhang Y, Shields CB, Zhang Y, Miklasz S, et al.
Ann Neurol. 2009 Mar; 65(3):304-15. PMID: 19334062. Abstract
Promotes functional recovery of demyelinated axons in rodent models
(6)
Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells.
Mi S, Miller RH, Tang W, Lee X, Hu B, Wu W, Zhang Y, Shields CB, Zhang Y, Miklasz S, et al.
Ann Neurol. 2009 Mar; 65(3):304-15. PMID: 19334062. Abstract
Monoclonal murine antibody mAb3B5, which recognizes mouse LINGO-1 and is a surrogate antibody for the human monoclonal Li81 (BIIB033) antibody, improves axon function in mice after experimental spinal cord demyelination
(13)
Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination.
Zhang Y, Zhang Y, Pepinsky B, Huang G, Shields LBE, Shields CB, Mi S
Exp Neurol. 2015 Feb 11. PMID: 25681574. Abstract
Monoclonal murine antibody mAb3B5, which recognizes mouse LINGO-1 and is a surrogate antibody for the human monoclonal Li81 (BIIB033) antibody, reduces lesion areas and increases the number of remyelinated axons in lesions in mice after experimental spinal cord demyelination
(13)
Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination.
Zhang Y, Zhang Y, Pepinsky B, Huang G, Shields LBE, Shields CB, Mi S
Exp Neurol. 2015 Feb 11. PMID: 25681574. Abstract
Regulatory and Commercial Status
Status for MS: 
Phase I results have been published
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Phase II trial is recruiting as of May, 2014
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Highest status achieved (for any condition): 
Phase II
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Other uses: 
Has been tested in acute optic neuritis in a Phase II trial; some positive results were reported (January 2015)
(12)
Biogen Idec reports positive top-line results from Phase 2 anti-LINGO-1 trial in people with acute optic neuritis
Biogen Idec, 8 Jan 2015
Accessed on 13 Jan 2015 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2452&M=NewsV2&PID=61997.
Administration: 
Intravenous infusion used in Phase I and Phase II trials
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Subcutaneous injection used in Phase I trial
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Negative effects: 
Adverse events occurred with similar frequencies in drug and placebo groups, and no serious adverse events occurred, in Phase I trials
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Commercial: 
Discovered by Biogen Idec
(1)
LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis.
Mi S, Hu B, Hahm K, Luo Y, Kam Hui E S, Yuan Q, Wong W M, Wang L, Su H, Chu T-H, et al.
Nat Med. 2007 Oct; 13(10):1228-33. Epub 2007 Sep 30. PMID: 17906634. Abstract
Clinical trials are sponsored by Biogen Idec
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
Biogen Idec, which is developing BIIB033, has changed its name to Biogen (23 March 2015)
(15)
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
Key Clinical Trials
Placebo-controlled Trials: 
Trial name: 
BIIB033 In Acute Optic Neuritis (RENEW) (press releases, January, April 2015)
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
(12)
Biogen Idec reports positive top-line results from Phase 2 anti-LINGO-1 trial in people with acute optic neuritis
Biogen Idec, 8 Jan 2015
Accessed on 13 Jan 2015 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2452&M=NewsV2&PID=61997.
(14)
Biogen Presents New Anti-LINGO-1 Phase 2 Acute Optic Neuritis Data Demonstrating Neurological Repair
Biogen, 14 Apr 2015
Accessed on 28 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-presents-new-anti-lingo-1-phase-2-acute-optic-neuritis-data-demonstra.
Phase: 
Phase II trial
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
Study Design: 
Industry-sponsored, multinational, randomized, double-blind, parallel-group, placebo-controlled trial to examine the efficacy of BIIB033 (6 doses of 100 mg per kg intravenous infusion, given once every 4 weeks for 20 weeks) in individuals experiencing their first episode of unilateral acute optic neuritis, with the primary outcome measure the change in optic nerve latency (time for a nerve signal to move from the retina to the visual cortex) at week 24 in the affected eye as compared with the baseline measure in the unaffected eye; secondary outcome measures included changes in the thickness of retinal layers and in low-contrast letter acuity at week 24 as compared with baseline
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
(12)
Biogen Idec reports positive top-line results from Phase 2 anti-LINGO-1 trial in people with acute optic neuritis
Biogen Idec, 8 Jan 2015
Accessed on 13 Jan 2015 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2452&M=NewsV2&PID=61997.
Disease Stage: 
Acute optic neuritis (first episode)
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
Enrollment/Number of Patients: 
82
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
Duration: 
24 weeks
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
Status/Outcome: 
Study completion date, October 2014
(11)
215ON201 BIIB033 In Acute Optic Neuritis (AON) (RENEW)
ClinicalTrials.gov, 14 Nov 2015
Accessed on 13 Jan 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01721161.
; BIIB033 was associated with a recovery of optic nerve latency (a 34% improvement as compared with placebo) at week 24, but not with a change in the thickness of retinal layers or with improved visual function
(12)
Biogen Idec reports positive top-line results from Phase 2 anti-LINGO-1 trial in people with acute optic neuritis
Biogen Idec, 8 Jan 2015
Accessed on 13 Jan 2015 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2452&M=NewsV2&PID=61997.
; at week 32, 12 weeks after the last dose, additional latency recovery was measured (a 41% improvement)
(14)
Biogen Presents New Anti-LINGO-1 Phase 2 Acute Optic Neuritis Data Demonstrating Neurological Repair
Biogen, 14 Apr 2015
Accessed on 28 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-presents-new-anti-lingo-1-phase-2-acute-optic-neuritis-data-demonstra.
Trial name: 
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY) (recruiting as of May 2014)
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Phase: 
Phase II trial
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Study Design: 
Company-sponsored, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging trial to examine the efficacy and safety of BIIB033 (intravenous infusion of 0, 3, 10, 30, or 100 mg per kg every 4 weeks) when used together with interferon beta-1a (Avonex, given by weekly intramuscular injections); the primary outcome measure is the percentage of participants who display improved neurophysical or cognitive function
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Disease Stage: 
Relapsing forms of MS
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Enrollment/Number of Patients: 
396 (estimated)
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Duration: 
84 weeks
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Status/Outcome: 
Estimated study completion date, June 2016
(10)
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)
ClinicalTrials.gov, 9 May 2014
Accessed on 2 Sep 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01864148.
Trial name: 
BIIB033 single ascending dose study in healthy volunteer subjects; Tran et al., Neurol. Neuroimmunol. Neuroinflammation, August 2014 trial
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Phase: 
Phase I trial
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Study Design: 
Company-sponsored, randomized, blinded, placebo-controlled, single-ascending dose trial to evaluate the safety and tolerability (primary outcome measures) and pharmacokinetics, serum antibody levels, and exploratory biomarkers (secondary outcome measures); single ascending doses (0.1 to 100 mg per kg) were administered by intravenous infusion or subcutaneous injection
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Disease Stage: 
Healthy individuals
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Enrollment/Number of Patients: 
72
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Duration: 
Up to 4 months
(4)
BIIB033 single ascending dose study in healthy volunteer subjects
ClinicalTrials.gov, 7 Jun 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01052506.
Status/Outcome: 
The drug was well tolerated; adverse events occurred at similar frequencies in the drug and placebo groups and no serious adverse events occurred; furthermore, anti-drug antibodies were detected in only one participant
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Trial name: 
Safety study of BIIB033 in subjects with multiple sclerosis; Tran et al., Neurol. Neuroimmunol. Neuroinflammation, August 2014 trial
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Phase: 
Phase I trial
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Study Design: 
Company-sponsored, randomized, blinded, placebo-controlled, serial-cohort, multiple ascending dose trial to determine the safety and tolerability (primary outcomes) and pharmacokinetics and potential biomarkers of activity (secondary outcomes) of two doses of drug (intravenous infusion of 0.3, 1, 3, 10, 30, 60, or 100 mg per kg) administered 14 days apart
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Disease Stage: 
RRMS or SPMS
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Enrollment/Number of Patients: 
47
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Duration: 
6 months
(5)
Safety study of BIIB033 in subjects with multiple sclerosis
ClinicalTrials.gov, 8 Nov 2012
Accessed on 14 Dec 2012 from http://clinicaltrials.gov/ct2/show/NCT01244139.
Status/Outcome: 
The drug was well tolerated; adverse events occurred at similar frequencies in the drug and placebo groups and no serious adverse events occurred
(8)
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, et al., 27 Aug 2014
Accessed on 27 Aug 2014 from http://nn.neurology.org/content/1/2/e18.short. doi:10.1212/NXI.0000000000000018.
Head-to-Head Trials: 
Other Trials: 
References
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
DOI: 
doi/10.7493/msdf.10.230.1