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Evidence that the anti-LINGO-1 monoclonal antibody BIIB033 protects against multifocal visual evoked potential amplitude loss in the fellow eye of subjects with unilateral acute optic neuritis
Author(s): ,
D. Cadavid
Affiliations:
Biogen, Cambridge, MA, United States
,
A. Klistorner
Affiliations:
University of Sydney; Macquarie University, Sydney, NSW, Australia
,
Y. Chai
Affiliations:
Biogen, Cambridge, MA, United States
,
L. Leocani
Affiliations:
Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Hospital, Milan, Italy
,
O. Aktas
Affiliations:
Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
,
H. Butzkueven
Affiliations:
Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
,
T. Ziemssen
Affiliations:
University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden
,
F. Ziemssen
Affiliations:
Universitätsklinikum Tübingen, Tubingen, Germany
,
J. Frederiksen
Affiliations:
Glostrup Hospital, University of Copenhagen, Glostrup, Denmark
,
L. Xu
Affiliations:
Biogen, Cambridge, MA, United States
on behalf of the RENEW Investigators
on behalf of the RENEW Investigators
Affiliations:
ECTRIMS Online Library. Cadavid D. Oct 10, 2015; 116697; 2286
Dr. Diego Cadavid
Dr. Diego Cadavid
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Abstract: 231

Type: Oral LB

Abstract Category: Invited / Oral LB / Poster LB

Background: The anti-LINGO-1 human monoclonal antibody BIIB033 is a potential first-in-class neuroreparative therapy, inclusive of remyelination, for inflammatory demyelinating CNS disorders such as MS. In RENEW (NCT01721161), improvement (vs placebo) in full-field and multifocal visual evoked potential (FF-/MF-VEP) latency for the affected eye was observed.

Objective: To investigate the efficacy of anti-LINGO-1 treatment on amplitude by assessing longitudinal changes between treatment groups in the RENEW MF-VEP substudy.

Methods: 81 subjects with a first unilateral acute optic neuritis (AON) episode were enrolled in RENEW and randomized to 100 mg/kg anti-LINGO-1 IV or placebo every 4 weeks (6 doses) within 28 days of symptom onset and after completion of high-dose steroids. Of these, 39 subjects (48%) at 13 clinics had MF-VEP assessment. Multiple visual field regions are stimulated simultaneously and recorded separately; MF-VEP was included as a substudy because of its superior sensitivity and reliability over FF-VEP. MF-VEP was performed at 4-8 week intervals for 32 weeks. Amplitude changes from baseline were assessed for the affected and fellow eyes and treatment differences determined using the mixed-effect model repeated measure.

Results: 18 subjects were randomized to placebo and 21 to anti-LINGO-1. Baseline mean (SD) fellow eye amplitude was 156.8 (57.3) nanovolts (nV; placebo) and 167.3 (34.6) nV (anti-LINGO-1). Corresponding values for the affected eye were markedly decreased: 87.2 (48.6) nV and 78.4 (57.6) nV, respectively. For the affected eye, adjusted mean change in MF-VEP amplitude at Week 32 was a recovery of 25.9 nV in the placebo and 48.2 nV in the anti-LINGO-1 groups, a difference of 22.3 nV (95% CI: −1.3, 45.9; P=0.0628). The fellow eye in the placebo group had an adjusted mean MF-VEP amplitude loss of 31.4 nV at Week 32 vs a 1.9 nV gain in the anti-LINGO-1 group, a preservation of amplitude of 33.3 nV with anti-LINGO-1 vs placebo (95% CI: 16.4, 50.3; P=0.0004).

Conclusions: Anti-LINGO-1 treatment in AON prevented the MF-VEP amplitude loss observed in the fellow eye visual pathway of placebo-treated subjects over 32 weeks; it also had possible positive effects on amplitude preservation on the affected eye. These results provide novel evidence of anti-LINGO-1 beneficial effects following AON, and additional proof of biological activity for anti-LINGO-1 besides the previously reported improvement of latency recovery for the affected eye.

Disclosure:

This study was supported by Biogen (Cambridge, MA, USA).

AK: consulting fees or research support from Biogen and Novartis;

LL: advisory board, speakers bureau and/or travel/research support from: Abbvie, Almirall, Biogen, Excemed, Genzyme, Merck Serono, Novartis;

OA: advisor fees, honoraria and/or research support from Bayer HealthCare, Biogen, Genzyme, MedImmune, Novartis, and Teva;

HB: consulting/advisor fees, honoraria and/or research support from Biogen, CSL Limited, Genzyme, Merck Serono, and Novartis;

TZ: consulting fees and/or research support from Almirall, Bayer HealthCare, Biogen, Genzyme, GlaxoSmithKline, Merck Serono, MSD, Novartis, Sanofi Aventis, Synthon, and Teva;

FZ: consulting fees and/or research support from Alimera, Allergan, Bayer HealthCare, and Novartis;

JF: served on scientific advisory boards and received funding for travel/honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Sanofi Aventis, and Teva, received speaker honoraria from Biogen, Merck Serono, and Teva, and served as an advisor on preclinical development for Takeda;

DC, YC, and LX: employees of and stockholders in Biogen.

Biogen provided funding for medical writing support in the development of this abstract. Becky Gardner (Excel Scientific Solutions, Horsham, UK) wrote the first draft of the abstract based on input from authors. Biogen reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract, and provided their final approval of all content.

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