Laquinimod for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with a high disability status

Inactive Publication Date: 2015-10-29
TEVA PHARMA IND LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]The subject invention also provides a method of reducing ambulatory deterioration in a human patient diagnosed to be afflicted with relapsing-remitting multiple sclerosis (RRMS) and having a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS), comprising periodically administering to only the patient diagnosed with RRMS and having a high baseline disability score an amount of laquinimod effective to reduce ambulatory deterioration.
[0014]The

Problems solved by technology

(Bjartmar, 2002) In addition to the inflammatory phase in MS, axonal loss occurs early in the course of the disease and can be extensive over time, leading to the subsequent development of progressive, permanent, neurologic impairment and, frequently, severe disability.
However, the mechanisms of action of each have been only partly elucidated.
However, the relationship between changes of the immune response induced by these agents and the clinical efficacy in MS is far from settled.
(Polman, 2005) However, the clinical significance of MRI brain lesion reduction alone is still unsettled.
Although MRI lesion

Method used

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  • Laquinimod for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with a high disability status
  • Laquinimod for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with a high disability status

Examples

Experimental program
Comparison scheme
Effect test

example 1

Clinical Trial (Phase III)—Assessment of Oral Laquinimod in Preventing Progression of MS

[0137]A multinational (24 countries), multicenter (approximately 139 sites), randomized, double-blinded, parallel-group, placebo-controlled clinical trial (“ALLEGRO” or MS-LAQ-301) was conducted to evaluate the efficacy, safety and tolerability of daily oral administration of laquinimod 0.6 mg in subjects with relapsing remitting multiple sclerosis (RRMS) for a 24 months duration.

[0138]One thousand one hundred and six (1106) patients were equally randomized to either laquinimod 0.6 mg or placebo and treated in a double-blind manner and baseline characteristics were balanced between groups. The primary endpoint of the study was the number of confirmed relapses during the double-blind treatment period, which corresponds to the annualized relapse rate (ARR−number of relapses divided by total exposure of all patients). Secondary endpoints included disability as measured by Expanded Disability Status ...

example 2

Clinical Trial (Phase III)—Benefit-Risk Assessment of Avonex® and Laquinimod

[0290]A multinational, multicenter, randomized, parallel-group, clinical trial is performed in subjects with RRMS (“BRAVO”). BRAVO was conducted to assess the efficacy, safety and tolerability of laquinimod over placebo in a double-blinded and rater-blinded design and of a reference arm of Interferon β-1a (Avonex®). The study was also conducted to perform a comparative benefit / risk assessment between oral laquinimod and injectable Interferon β-1a (Avonex®).

[0291]The primary objective of the study was to assess the efficacy of 0.6 mg daily dose of laquinimod in subjects with RRMS as measured by the number of confirmed relapses during the treatment period. Secondary objectives of the study included assessing the effect of 0.6 mg daily dose of laquinimod on the accumulation of disability, as assessed by the MSFC score at the end of the treatment period; assessing the effect of 0.6 mg daily dose of laquinimod on...

example 3

Post Hoc Analysis of ALLEGRO and BRAVO Trials: Evaluation of Laquinimod Efficacy in Patient Subgroups

Introduction

[0486]Natural history data show that once EDSS of 3 is reached, disability progression becomes both more likely and more rapid (Pittock et al. Neurology 2004; 62:51-9; Pittock et al. Neurology 2004; 62:601-6; Leray et al. Brain 2010; 133:1900-1913). At EDSS>3, chronic diffuse inflammation may be a more important driver of disability.

[0487]Patients with an EDSS score of ≦3 are fully ambulatory; however gait dysfunction is common in multiple sclerosis and is a key component of disability progression beyond this stage. Patients beyond this stage experience growing motor impairment. Patients with an EDSS of 3.5 are fully ambulatory but already manifest moderate disability in selected functional systems. Patients with an EDSS of 4 experience some restriction in ambulation, but are up and about most of the day despite clear neurological dysfunction. Subsequent EDSS progression ...

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Abstract

This invention provides a method for treating or for reducing ambulatory deterioration in a human patient diagnosed to be afflicted with relapsing-remitting multiple sclerosis (RRMS) and having a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS), comprising periodically administering to only the patient diagnosed with RRMS and having a high baseline disability score an amount of laquinimod effective to treat the patient or to reduce ambulatory deterioration. This invention further provides pharmaceutical compositions and packages comprising an effective amount of laquinimod for treating a human patient diagnosed to be afflicted with RRMS and having a high baseline disability score according to the EDSS.

Description

[0001]This application claims benefit of U.S. Provisional Application No. 61 / 985,886, filed Apr. 29, 2014, U.S. Provisional Application No. 62 / 046,561, filed Sep. 5, 2014, U.S. Provisional Application No. 62 / 119,506, filed Feb. 23, 2015, and U.S. Provisional Application No. 62 / 139,978, filed Mar. 30, 2015, the entire contents of each of which are hereby incorporated by reference herein.[0002]Throughout this application, various publications are referred to by first author and year of publication. Full citations for these publications are presented in a References section immediately before the claims. Disclosures of the publications cited in the References section in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as of the date of the invention described herein.BACKGROUND[0003]Multiple Sclerosis (MS) is a neurological disease affecting more than 1 million people worldwide. It is the most common cause o...

Claims

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Application Information

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IPC IPC(8): A61K31/4704A61B5/00A61B5/11A61J1/00
CPCA61K31/4704A61B5/112A61B5/4082A61J1/00A61K31/47A61K38/215A61P25/00A61P25/14A61P25/28A61P29/00A61P37/00A61P37/02A61P43/00A61K9/0053A61K45/06A61B5/4839A61J7/0076
Inventor KNAPPERTZ, VOLKER
Owner TEVA PHARMA IND LTD
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