Delving into the Latest Updates on Refanezumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-MAG monoclonal antibody

+ [1]

Target

MAG

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

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Sequence Code 17117615L

Source: *****

BACKGROUND AND OBJECTIVESPolyneuropathy associated with an immunoglobulin M (IgM) monoclonal gammopathy is characterized by slowly progressive, predominantly distal sensorimotor deficits, sensory ataxia, and electrophysiologic features of demyelination. IgM antibodies against myelin-associated glycoprotein (MAG) are present in serum from most patients. Nerve damage most likely results from the concerted action of binding of anti-MAG antibodies to nerves, followed by complement activation. The interaction of anti-MAG antibodies with complement activation and their relation to clinical characteristics have not been studied in detail. We studied the correlation among anti-MAG antibody titers, complement activation, and IgM-associated polyneuropathy disease severity.METHODSWe used serum samples from 101 patients with IgM-associated polyneuropathy to assess IgM anti-MAG titers by ELISA and antibody-mediated complement deposition using both an ELISA-based system and a cell-based system of primate peripheral nerve slides. We studied correlations of complement activation with anti-MAG ELISA titers and clinical characteristics.RESULTSIgM anti-MAG titers varied from negative to strongly positive. Complement deposition in the ELISA-based system correlated significantly with anti-MAG antibody titer (Spearman rho 0.80; p < 0.0001) despite large variability between serum samples with comparable anti-MAG titers. This variability was even larger in the cell-based assay, which also showed complement deposition in IgM anti-MAG negative patients, indicating the presence of autoantibodies directed against epitopes other than MAG in a subset of patients with IgM-associated polyneuropathy. Clinical characteristics did not correlate with anti-MAG titers or complement activation.DISCUSSIONAnti-MAG antibody titers correlate with the level of complement activation in both ELISA and cell-based systems. However, clinical characteristics of IgM-associated polyneuropathy do not or only weakly correlate with titers or the level of complement deposition. The lack of clear correlations between complement activation and clinical characteristics does, at this stage, not support the use of complement inhibitors in the treatment of IgM-associated polyneuropathy.

01 Jan 2024·British Journal of Haematology

Clinical and clonal characteristics of monoclonal immunoglobulin M‐associated type I cryoglobulinaemia

Article

Author: Gupta, Rajeev ; Vos, Josephine M I ; Patel, Aisha ; Kwakernaak, Arjan J ; D'Sa, Shirley ; Japzon, Nicole ; Kyriakou, Charalampia ; Wechalekar, Ashutosh D ; Khwaja, Jahanzaib ; Rismani, Ali ; Salter, Simon ; Pluimers, Tessa E

SummaryMonoclonal immunoglobulin M‐associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9‐year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non‐Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM‐associated disorders (including cold agglutinin disease [CAD], anti‐MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild‐type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin‐related symptoms alone at a median of 38 days (range: 6–239) from cryoglobulin detection. At a median follow‐up of 3 years (range: 0–10), 3‐year cryoglobulinaemia‐treatment‐free survival was 77% (95% CI: 68%–84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia‐related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62–341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13–7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.

01 Feb 2023·European Journal of NeurologyQ2 · MEDICINE

A diagnostic score for anti‐myelin‐associated‐glycoprotein neuropathy or chronic inflammatory demyelinating polyradiculoneuropathy in patients with anti‐myelin‐associated‐glycoprotein antibody

Q2 · MEDICINE

Article

Author: Bianchi, Elisa ; Marfia, Girola A. ; Cocito, Dario ; Doneddu, Pietro E. ; Giannotta, Claudia ; Briani, Chiara ; Cosentino, Giuseppe ; Ruiz, Marta ; Nobile‐Orazio, Eduardo ; Benedetti, Luana ; Filosto, Massimiliano ; Liberatore, Giuseppe ; Manganelli, Fiore

AbstractBackground and purposeA diagnostic score was developed to discriminate anti‐myelin‐associated‐glycoprotein (MAG) neuropathy from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and applied it to patients with atypical anti‐MAG neuropathy.MethodsThe clinical and electrophysiological features of patients with a diagnosis of typical anti‐MAG neuropathy were compared to those of patients with a diagnosis of CIDP. The association of each feature with the diagnosis was assessed in the two groups. Features showing a significant association with the diagnosis were included in a multivariable logistic regression model and adjusted odds ratios were estimated for each feature. A score ranging from 1 to 3 was applied to each feature based on the magnitude of the estimated odds ratios. The score was then applied to patients with a clinical diagnosis of CIDP who also had high anti‐MAG antibody titers (CIDP‐MAG).ResultsThirty‐one anti‐MAG neuropathy patients, 45 typical CIDP patients and 16 CIDP‐MAG patients were included. Scores in anti‐MAG antibody patients ranged from 1 to 5 and in CIDP patients from −7 to −1. Using the score, 4/16 CIDP‐MAG patients were diagnosed to have anti‐MAG neuropathy and 12/16 patients to have CIDP. Response to intravenous immunoglobulin in the CIDP‐MAG patients classified as CIDP was similar to that of definite CIDP patients and higher than that of anti‐MAG neuropathy patients.ConclusionsOur score allowed an accurate discrimination to be made, amongst patients with anti‐MAG antibodies, of those affected by CIDP and the patients with anti‐MAG neuropathy. This score may help proper treatment to be chosen for patients with anti‐MAG antibodies with a CIDP‐like presentation.

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	DE	GSK Plc	18 May 2013
Ischemic stroke	Phase 2	GB	GSK Plc	18 May 2013
Ischemic stroke	Phase 2	US	GSK Plc	18 May 2013
Ischemic stroke	Phase 2	CA	GSK Plc	18 May 2013
Ischemic Attack, Transient	Phase 2	DE	GSK Plc	08 Jul 2009
Ischemic Attack, Transient	Phase 2	CA	GSK Plc	08 Jul 2009
Ischemic Attack, Transient	Phase 2	US	GSK Plc	08 Jul 2009
Stroke	Phase 2	DE	GSK Plc	08 Jul 2009
Stroke	Phase 2	CA	GSK Plc	08 Jul 2009
Stroke	Phase 2	US	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	ybhkwwyjiy(wkghpziuno) = qzegrvccql tvdaqgomgi (brbrhjywcn, vvwgqgvaru - cmilkzpxdz) View more	-	16 Oct 2017
NCT01808261 (104615, CTgov)	Phase 2	Ischemic stroke	134	Placebo	jxelosxpru(afqykickhe) = zjlhkazxvl hecwewkprm (tfjcwsvixt, fplvgqytdj - owplgvxuad) View more	-	03 Oct 2017
AAN2013	Not Applicable	Stroke myelin-associated glycoprotein (MAG) \| S100β	42	GSK249320 1 mg/kg	gatrmwuknc(amjxqnlwfg) = bierpnjmaz wggicbraki (ugchgcyqkn ) View more	Positive	12 Feb 2013
AAN2013	Not Applicable	Stroke myelin-associated glycoprotein (MAG) \| S100β	42	GSK249320 5 mg/kg	gatrmwuknc(amjxqnlwfg) = gedejlqbsu wggicbraki (ugchgcyqkn ) View more	Positive	12 Feb 2013