Delving into the Latest Updates on Dirucotide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Dirucotide (USAN), Dirucotide Acetate

+ [3]

Target

MBP

Mechanism

MBP modulators(Myelin basic protein modulators)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Multiple SclerosisMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-Remitting+ [1]

Originator Organization

University of Alberta

Active Organization-

Inactive Organization

Eli Lilly & Co.

Medwell Capital Corp.BioMS Technology US Corp

+ [2]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC92H141N25O26

InChIKeyRCTCWZRPYFBGLQ-WMCRPSJMSA-N

CAS Registry152074-97-0

Gene Sequence

Sequence Code 4657725

Source: *****

Background Enhanced prediction of progression in secondary progressive multiple sclerosis (SPMS) could improve clinical trial design. Machine learning (ML) algorithms are methods for training predictive models with minimal human intervention. Objective To evaluate individual and ensemble model performance built using decision tree (DT)-based algorithms compared to logistic regression (LR) and support vector machines (SVMs) for predicting SPMS disability progression. Methods SPMS participants ( n = 485) enrolled in a 2-year placebo-controlled (negative) trial assessing the efficacy of MBP8298 were classified as progressors if a 6-month sustained increase in Expanded Disability Status Scale (EDSS) (≥1.0 or ≥0.5 for a baseline of ≤5.5 or ≥6.0 respectively) was observed. Variables included EDSS, Multiple Sclerosis Functional Composite component scores, T2 lesion volume, brain parenchymal fraction, disease duration, age, and sex. Area under the receiver operating characteristic curve (AUC) was the primary outcome for model evaluation. Results Three DT-based models had greater AUCs (61.8%, 60.7%, and 60.2%) than independent and ensemble SVM (52.4% and 51.0%) and LR (49.5% and 51.1%). Conclusion SPMS disability progression was best predicted by non-parametric ML. If confirmed, ML could select those with highest progression risk for inclusion in SPMS trial cohorts and reduce the number of low-risk individuals exposed to experimental therapies.

01 Jan 2019·Multiple Sclerosis Journal - Experimental, Translational and Clinical

Effect of different doses of gadolinium contrast agent on clinical outcomes in MS

Article

Author: Taylor, Carolyn ; Traboulsee, Anthony L ; Tam, Roger ; Freedman, Mark S ; Kang, Heejun ; Li, David KB ; Ackermans, Nathalie ; Carruthers, Robert ; Kolind, Shannon

Objective The objective of this paper is to evaluate potential dose-dependent adverse effects of gadolinium-based contrast agents (GBCAs) on MS progression. Methods Outcomes from a cohort of 612 secondary progressive MS (SPMS) patients, enrolled in a two-year, placebo-controlled (negative) trial assessing the efficacy of MBP8298, were acquired. Patients received one to four (infrequent cohort; IFR) or 5–11 (frequent cohort; FR) GBCA injections between week 4 and week 104. The primary outcome was the change in Expanded Disability Status Scale (EDSS) and time to confirmed EDSS progression. Secondary outcomes included the changes in the Multiple Sclerosis Functional Composite (MSFC), Timed 25-Foot Walk (T25FW), 9-Hole-Peg Test (9HPT), and Paced Auditory Serial Addition Test (PASAT) from baseline to week 104. Results The 512 IFR and 100 FR participants showed no differences in baseline demographics or disease history. The mean change from baseline to week 104 in EDSS was +0.21 (IFR) and +0.13 (FR); MSFC –0.38 (IFR) and –0.14 (FR); T25FW +1.28 (IFR) and +0.55 (FR); 9HPT –0.06 (IFR) and –0.08 (FR); and PASAT +0.22 (IFR) and +0.20 (FR). The FR to IFR progression hazard ratio equaled 0.68 ( p = 0.09). There were no significant differences in any of the outcomes between the two cohorts. Conclusion There were no differences in the disability progression measures between the two cohorts, indicating that gadolinium does not result in greater clinical worsening in SPMS after a two-year period.

01 Sep 2017·Journal of Chromatography AQ2 · CHEMISTRY

Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange centrifugal partition chromatography

Q2 · CHEMISTRY

Article

Author: Jean-Hugues Renault ; Leslie Boudesocque ; Jean-Marc Nuzillard ; Luciano Forni ; Agathe Martinez ; Matthieu Giraud

Dirucotide is a synthetic drug candidate for the treatment of multiple sclerosis. This 17-aminoacid peptide was successfully purified by ion exchange centrifugal partition chromatography. The optimized conditions involved the biphasic methyl tert-butyl ether/acetonitrile/n-butanol/water (2:1:2:5, v/v) solvent system in the descending mode, the di(2-ethylhexyl)phosphoric acid cation-exchanger with an exchanger (di(2-ethylhexyl)phosphoric acid)/dirucotide mole ratio of 100 and Ca²⁺ ions in aqueous solution as displacer. Critical impurities were efficiently eliminated and dirucotide was recovered in high yield and purity (69% and 98%, respectively) and with a productivity of 2.29g per liter of stationary phase per hour.

100 Deals associated with Dirucotide

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External Link

KEGG	Wiki	ATC	Drug Bank
D09396	Dirucotide	-	DB04921

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	Phase 3	EE	Eli Lilly & Co.	01 Dec 2004
Multiple Sclerosis, Secondary Progressive	Phase 3	FI	Eli Lilly & Co.	01 Dec 2004
Multiple Sclerosis, Secondary Progressive	Phase 3	GB	Eli Lilly & Co.	01 Dec 2004
Multiple Sclerosis, Secondary Progressive	Phase 3	NL	Eli Lilly & Co.	01 Dec 2004
Multiple Sclerosis, Secondary Progressive	Phase 3	SE	Eli Lilly & Co.	01 Dec 2004
Multiple Sclerosis	Phase 3	-	University of Alberta	-
Multiple Sclerosis	Phase 3	US	Medwell Capital Corp.	-
Multiple Sclerosis	Phase 3	CA	Medwell Capital Corp.	-
Multiple Sclerosis	Phase 3	EU	Medwell Capital Corp.	-
Multiple Sclerosis	Phase 3	-	Autoimmune Technologies LLC	-