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Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-MAG monoclonal antibody

+ [1]

Target

MAG

Action

inhibitors

Mechanism

MAG inhibitors(Myelin-associated glycoprotein inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication-

Inactive Indication

Ischemic Attack, TransientIschemic strokeStroke

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 319372583H

Source: *****

Sequence Code 17117615L

Source: *****

Previous case reports and studies have shown that anti-myelin-associated glycoprotein (MAG) antibody can be detected in patients with polyneuropathy without any detectable M-protein. Nevertheless, the frequency of and related factors have not yet been adequately investigated. The objectives of this study are to examine the prevalence of anti-MAG antibody in patients with demyelinating neuropathy without M-protein and to determine their clinical characteristics. From January, 2004, to September, 2016, consecutive patients with chronic demyelinating neuropathy were recruited. Anti-MAG antibody presence was tested at the first evaluation. We determined the prevalence of anti-MAG antibody without M-protein among included patients and evaluated the clinical characteristics. A total of 44 patients were included in the present study (12 women; median age at first visit 60 years [interquartile range 47-67 years]; median duration between onset and first visit 9 months [3-26 months]). M-protein was found in eight patients (18%) at the first evaluation. Anti-MAG antibody was present in 2 of remaining 36 (5.6 [95% confidence interval 0-13.0] %) patients without M-protein. Patients with anti-MAG antibody exhibited slowly progressive and distal dominant neuropathy with elevated serum IgM levels and refractory to immunotherapy. There were no differences in clinical features between patients having anti-MAG antibody without M-protein, and those with M-protein. One patient with the anti-MAG antibody showed a delayed appearance of M-protein during a 4-year follow-up after diagnosis. The prevalence of the anti-MAG antibody in chronic demyelinating neuropathy without any detectable M-protein was 5.6%. Anti-MAG antibody may be detectable earlier than M-protein.

01 Mar 2017·StrokeQ1 · MEDICINE

Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients

Q1 · MEDICINE

Article

Author: Simeoni, Monica ; Thompson, Thomas R. ; Russell, Colleen K. ; Enney, Lori A. ; Cramer, Steven C.

Background and Purpose—One class of poststroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein. The purpose of the current study was to extend preclinical and clinical findings of GSK249320, a humanized monoclonal antibody to myelin-associated glycoprotein with disabled Fc region, to explore effects on motor outcomes poststroke.Methods—In this phase IIb double-blind, randomized, placebo-controlled study, patients at 30 centers with ischemic stroke 24 to 72 hours prior and gait deficits were randomized to 2 IV infusions of GSK249320 or placebo. Primary outcome measure was change in gait velocity from baseline to day 90.Results—A total of 134 subjects were randomized between May 2013 and July 2014. The 2 groups were overall well matched at baseline. The study was stopped at the prespecified interim analysis because the treatment difference met the predefined futility criteria cutoff; change in gait velocity to day 90 was 0.55±0.46 (mean±SD) in the GSK249320 group and 0.56±0.50 for placebo. Secondary end points including upper extremity function were concordant. The 2 IV infusions of GSK249320 were well tolerated. No neutralizing antibodies to GSK249320 were detected.Conclusions—GSK249320, within 72 hours of stroke, demonstrated no improvement on gait velocity compared with placebo. Possible reasons include challenges translating findings into humans and no direct evidence that the therapy reached the biological target. The antibody was well tolerated and showed low immunogenicity, findings potentially useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways to improve recovery from stroke.Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01808261.

01 Jun 2015·StrokeQ1 · MEDICINE

Effects of Postinfarct Myelin-Associated Glycoprotein Antibody Treatment on Motor Recovery and Motor Map Plasticity in Squirrel Monkeys

Q1 · MEDICINE

Article

Author: Cramer, Steven C. ; Nudo, Randolph J. ; Frost, Shawn B. ; Zoubina, Elena ; Plautz, Erik J. ; Barbay, Scott

Background and Purpose—New insights into the brain’s ability to reorganize after injury are beginning to suggest novel restorative therapy targets. Potential therapies include pharmacological agents designed to promote axonal growth. The purpose of this study was to test the efficacy of one such drug, GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule, myelin-associated glycoprotein, to facilitate recovery of motor skills in a nonhuman primate model of ischemic cortical damage.Methods—Using a between-groups repeated-measures design, squirrel monkeys were randomized to 1 of 2 groups: an experimental group received intravenous GSK249320 beginning 24 hours after an ischemic infarct in motor cortex with repeated dosages given at 1-week intervals for 6 weeks and a control group received only the vehicle at matched time periods. The primary end point was a motor performance index based on a distal forelimb reach-and-retrieval task. Neurophysiological mapping techniques were used to determine changes in spared motor representations.Results—All monkeys recovered to baseline motor performance levels by postinfarct day 16. Functional recovery in the experimental group was significantly facilitated on the primary end point, albeit using slower movements. At 7 weeks post infarct, motor maps in the spared ventral premotor cortex in the experimental group decreased in area compared with the control group.Conclusions—GSK249320, initiated 24 hours after a focal cortical ischemic infarct, facilitated functional recovery. Together with the neurophysiological data, these results suggest that GSK249320 has a substantial biological effect on spared cortical tissue. However, its mechanisms of action may be widespread and not strictly limited to peri-infarct cortex and nearby premotor areas.

100 Deals associated with Refanezumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Refanezumab	-	DB14908

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ischemic stroke	Phase 2	United States	GSK Plc	18 May 2013
Ischemic stroke	Phase 2	United Kingdom	GSK Plc	18 May 2013
Ischemic stroke	Phase 2	Canada	GSK Plc	18 May 2013
Ischemic stroke	Phase 2	Germany	GSK Plc	18 May 2013
Ischemic Attack, Transient	Phase 2	Germany	GSK Plc	08 Jul 2009
Ischemic Attack, Transient	Phase 2	Canada	GSK Plc	08 Jul 2009
Ischemic Attack, Transient	Phase 2	United States	GSK Plc	08 Jul 2009
Stroke	Phase 2	United States	GSK Plc	08 Jul 2009
Stroke	Phase 2	Canada	GSK Plc	08 Jul 2009
Stroke	Phase 2	Germany	GSK Plc	08 Jul 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00833989 (MAG111539, CTgov)	Phase 2	Stroke \| Ischemic Attack, Transient	42	PLACEBO	piaijyqwbt(mnztandtlx) = sfqyymlojw eoietoabys (bynqtnybzh, euuzhmrklz - dhlpogguek) View more	-	16 Oct 2017
NCT01808261 (104615, CTgov)	Phase 2	Ischemic stroke	134	Placebo	vlzjbztpmk(kxqxiuasdi) = kmfcsqsukp hslnisyawl (lfbxiqowhg, noswzozpxb - ivujzgbqlf) View more	-	03 Oct 2017
AAN2013	Not Applicable	Stroke myelin-associated glycoprotein (MAG) \| S100β	42	GSK249320 1 mg/kg	tinjombruj(zakpcosrjy) = fpwxzhkeam xoexyhtnox (umtxdxuwwc ) View more	Positive	12 Feb 2013
AAN2013	Not Applicable	Stroke myelin-associated glycoprotein (MAG) \| S100β	42	GSK249320 5 mg/kg	tinjombruj(zakpcosrjy) = bhbzsijmim xoexyhtnox (umtxdxuwwc ) View more	Positive	12 Feb 2013

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Biosimilar

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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Refanezumab

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation