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

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...

AI Technical Summary

Benefits of technology

The present invention provides a method for reducing the deterioration of a human patient with relapsing-remitting multiple sclerosis (RRMS) who has a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS). This method involves periodically administering to the patient an effective amount of laquinimod to reduce theambulatory deterioration. This invention also reduces the mobility deterioration in an RMS patient who has impaired mobility, by periodically administering to them an effective amount of laquinimod.

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 lesions are used as the primary outcome measure in some studies, others have suggested that correlation between MRI abnormalities and clinical disease activity in RRMS patients is weak and that such measurement should be used as secondary outcomes rather than as surrogate markers of clinical responses.

(Rudick, 1999; Miki, 1999; Barkhof, 1999) Further, according to pharmaceutical regulatory bodies such as the European Medicines Agency (EMEA), the correlation between MRI results and clinical outcomes has not been proved strong enough so as to accept MRI results as validated surrogate endpoint in pivotal studies.

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