Abstract Details

Title Evidence of Remyelination with the Anti-LINGO-1 Monoclonal Antibody BIIB033 After Acute Optic Neuritis

Topic Multiple Sclerosis

Presentation(s) (-)

Poster/Presentation
Number 008

Objective

Background BIIB033, a fully human anti-LINGO-1 monoclonal antibody, showed efficacy in preclinical models of remyelination and was well tolerated in Phase 1 studies.

Design/Methods RENEW (NCT01721161) was a randomized, double-blind, placebo-controlled, parallel-group study in subjects with first unilateral acute optic neuritis episode. Subjects (18 to 50 years) completed treatment with high-dose steroids and were then randomized 1:1 to 100 mg/kg BIIB033 IV or placebo once every 4 weeks (wks; 6 doses total) and followed up to Week 32. Remyelination was evaluated by recovery of optic nerve conduction latency using full-field visual evoked potential (FF-VEP) compared with the unaffected fellow eye at baseline. Neuroprotection was studied by measuring the thickness of the retinal nerve fiber layer and ganglion cell layer using spectral-domain optical coherence tomography (SD-OCT), and change in low-contrast letter acuity (LCLA). Between-treatment comparisons were evaluated by ANCOVA and MMRM in the per-protocol (PP) and intent-to-treat (ITT) populations. Safety/tolerability were also evaluated.

Results Eighty-two subjects received BIIB033 (ITT N=41; PP N=33) or placebo (ITT N=41; PP N=36). In the PP population BIIB033-treated patients showed a significantly improved average difference in latency recovery vs placebo: 7.55 msec at 24wks (ANCOVA p=0.05) and 9.13 msec (MMRM p=0.01) at 32wks. Corresponding differences in the ITT population were 3.48 msec (p=0.33) at 24wks and 6.06 msec (p=0.07) at 32wks. During this period, no differences were observed in SD-OCT and LCLA. Overall incidence and severity of adverse events (AEs) were comparable across treatment arms. Treatment-related serious AEs were infusion-related hypersensitivity reactions (N=2) and asymptomatic transient elevation in liver transaminases (N=1).

Conclusions RENEW is the first clinical trial reporting on the efficacy of BIIB033. The observed shortening of the FF-VEP provides evidence of proof of biology for remyelination.

Authors/Disclosures
Diego Cadavid, MD, FAAN (Verge Genomics)	Dr. Cadavid has received personal compensation for serving as an employee of Verge Genomics. Dr. Cadavid has received personal compensation for serving as an employee of X4 Pharmaceuticals. Dr. Cadavid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Cadavid has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. Cadavid has stock in Verge Genomics.
Laura J. Balcer, MD, MSCE, FAAN (NYU Grossman School of Medicine)	Dr. Balcer has received personal compensation for serving as an employee of North American Neuro-Ophthalmology Society. An immediate family member of Dr. Balcer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Children's Hospital of Philadelphia.
Steven Galetta, MD, FAAN (NYU Langone Medical Center)	Dr. Galetta has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��