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.

1 . A method of treating, or for reducing ambulatory deterioration or mobility deterioration in, a human patient diagnosed to be afflicted with relapsing-remitting multiple sclerosis (RRMS) and having 1) a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS) or 2) impaired mobility, comprising 1) periodically administering to only the patient diagnosed with RRMS and having a high baseline disability score an amount of laquinimod effective to treat, or to reduce ambulatory deterioration in, the patient, or 2) periodically administering to only the patient diagnosed with RRMS and having impaired mobility an amount of laquinimod effective to treat, or to reduce mobility deterioration in, the patient. 
     
     
         2 . The method of  claim 1 , comprising
 a) diagnosing the patient as having a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS), and   b) administering to the patient an amount of laquinimod effective to treat the patient only if the patient has been diagnosed as having a high baseline disability score.   
     
     
         3 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the amount of laquinimod is effective to reduce the patient's relapse rate, reduce the patient's accumulation of physical disability, and/or reduce deterioration of the patient's ambulation. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 6 , wherein the accumulation of physical disability is assessed by the patient's Multiple Sclerosis Functional Composite (MSFC) score or the time to confirmed disease progression (CDP) as measured by EDSS score, and/or ambulation is assessed by the patient's Timed-25 foot walk test score. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The method of  claim 8 , wherein the patient has a baseline EDSS score of 3.5-5.0 and CDP is a 1 point increase of the baseline EDSS score, or wherein the patient has a baseline EDSS score of greater than 3.5, greater than 4.0, greater than 4.5, greater than 5.0, or greater than 5.5, and CDP is a 1 point increase of the baseline EDSS score, or wherein the patient has a baseline EDSS score of 5.5 or greater and CDP is a 0.5 point increase of the baseline EDSS score. 
     
     
         14 - 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the patient:
 has been diagnosed with a baseline EDSS score of greater than 3.5, greater than 4.0, greater than 4.5, greater than 5.0, or greater than 5.5, or has been diagnosed with a baseline EDSS score of 3.5-5.5, or   is naïve to an RRMS treatment, or naïve to laquinimod treatment, or naïve to 0.3 mg/day, 0.6 mg/day or 1.2 mg/day laquinimod treatment.   
     
     
         24 - 29 . (canceled) 
     
     
         30 . The method of  claim 1 , wherein laquinimod is laquinimod sodium, and/or is administered orally, and/or is administered daily, and/or wherein laquinimod is administered at a daily dose of 0.1-2.5 mg laquinimod, a daily dose of 0.6 mg laquinimod or a daily dose of 1.2 mg laquinimod. 
     
     
         31 - 35 . (canceled) 
     
     
         36 . The method of  claim 1 , wherein the periodic administration is for a period of greater than 24 weeks. 
     
     
         37 . The method of  claim 1 , wherein laquinimod is administered as monotherapy for RRMS or is administered as adjunct therapy with an other RRMS treatment. 
     
     
         38 - 43 . (canceled) 
     
     
         44 . A package comprising:
 a) a pharmaceutical composition comprising an amount of laquinimod; and   b) instruction for use of the pharmaceutical composition to treat only a human patient diagnosed to be afflicted with relapsing-remitting multiple sclerosis (RRMS) and having a) a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS), or b) impaired mobility, or c) worsening MS.   
     
     
         45 . The package of  claim 44 , wherein the high baseline disability score is a baseline EDSS score of greater than 3. 
     
     
         46 . The package of  claim 44 , which is a therapeutic package for dispensing to, or for use in dispensing to, only a human patient diagnosed to be afflicted with relapsing-remitting multiple sclerosis (RRMS) and having
 1) a high baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS) or 2) impaired mobility, or 3) worsening MS, which comprises:   a) one or more unit doses, each such unit dose comprising an amount of laquinimod thereof, wherein the amount of said laquinimod in said unit dose is effective, upon administration to said patient, to treat the patient, and   b) a finished pharmaceutical container therefor, said container containing said unit dose or unit doses, said container further containing or comprising labeling directing the use of said package in the treatment of said patient.   
     
     
         47 . The therapeutic package of  claim 46 , wherein the high baseline disability score is a baseline EDSS score of greater than 3. 
     
     
         48 - 52 . (canceled) 
     
     
         53 . The method of  claim 1 , wherein mobility is assessed by the patient's Timed-25 foot walk test score, the MSWS-12 self-report questionnaire, the Ambulation Index, the Six-Minute Walk (6MW) Test or the LEMMT Test, and/or wherein the mobility impairment is an ambulatory impairment, and/or wherein the patient is not ambulatory. 
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . The method of  claim 1 , comprising
 a) diagnosing the patient as having a mobility impairment as assessed by the patient's Timed-25 foot walk test score, and   b) administering to the patient an amount of laquinimod effective to treat the patient only if the patient has been diagnosed as having a mobility impairment.   
     
     
         57 - 100 . (canceled) 
     
     
         101 . The package of  claim 44 , wherein the mobility impairment is an ambulatory impairment, and/or wherein the patient is not ambulatory. 
     
     
         102 . (canceled) 
     
     
         103 . (canceled) 
     
     
         104 . A method of treating a human patient diagnosed to be afflicted with RRMS and having worsening MS, comprising periodically administering to only the patient diagnosed with RRMS and having worsening MS an amount of laquinimod effective to treat the patient. 
     
     
         105 . The method of  claim 104 , wherein the patient has a baseline disability score according to the Kurtzke Expanded Disability Status Scale (EDSS) of greater than 3.0. 
     
     
         106 . The method of  claim 104 , wherein laquinimod is laquinimod sodium, and/or is administered orally, and/or is administered daily, and/or is administered at a daily dose of 0.1-2.5 mg, 0.6 mg or 1.2 mg laquinimod. 
     
     
         107 - 111 . (canceled) 
     
     
         112 . The method of  claim 104 , wherein laquinimod is administered as monotherapy for RRMS, or is administered as adjunct therapy with another RRMS treatment. 
     
     
         113 - 119 . (canceled)