REPORT FROM THE 67TH AMERICAN ACADEMY OF NEUROLOGY (AAN) ANNUAL MEETING – WASHINGTON DC, APRIL 18-25, 2015 – BIIB033 is a monoclonal antibody targeting LINGO-1 (leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitor receptor-interacting protein-1), which is expressed on neurons and oligodendrocytes and which impedes oligodendrocyte differentiation and myelination.
No serious adverse events were reported in phase I testing (Tran et al. Neurol Neuroimmunol Neuroinflamm 2014;1:e18).
RENEW is the first of two trials to investigate the impact of BIIB033 on remyelination (Cadavid et al. AAN 2015; abstract P7.202). A total of 82 subjects with optic neuritis received IV methylprednisolone prior to randomization to BIIB033 100 mg/kg IV q4wks or placebo for 20 weeks (6 treatments). The primary endpoint was optic nerve conduction latency at week 24 in the affected versus unaffected fellow eye at baseline, as assessed by full-field visual evoked potential (FF-VEP).
In the intention-to-treat (ITT) analysis, treatment was not associated with significant differences in any of the endpoints, including optic nerve latency (p=0.33), change in retinal nerve fibre thickness (p=0.19), or change in low-contrast letter acuity (LCLA) (1.25% and 2.5% Sloan letter charts using the affected eye’s baseline value) (1.5%, p=0.54; 2.5%, p=0.77). Statistical significance was achieved in optic nerve latency in a per-protocol analysis (n=69). FF-VEP latency recovery to normal or near-normal was more frequent with treatment versus placebo (53% vs. 26%).
A separate analysis of vision-related quality of life found that both the treated subjects and placebo subjects experienced substantial improvements from baseline; no significant difference between the BIIB003 and placebo groups was observed at any time point (Petrillo et al. AAN 2015; abstract P7.213). The proportion of patients with >4-point improvement in the Visual Functioning Questionnaire-25 (VFQ-25) composite score was numerically higher with placebo versus BIIB003 (74% vs. 69%). The authors noted that it is unclear if any of the items included on the VFQ-25 are sensitive to the effects of remyelination of the optic nerve.
The SYNERGY phase II trial will evaluate BIIB003 as an add-on to beta-interferon-1a IM in patients with RRMS or SPMS (Cadavid et al. AAn 2015; abstract P7.204). The primary endpoint will be the proportion of people with confirmed improvement on one or more components of a composite measure (EDSS, T25FW, 9HPT, PASAT-3). To date, 330 RRMS and 88 SPMS patients have been randomized.
Guest Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada