3-(4-((4-(morpholinomethyl-benzyl)oxy)-1 -oxoisoindolin-2-yl)piperidine-2,6-dione for the treatment of systemic lupus erythematosus

Abstract

Provided herein are methods of using compounds and compositions for treating, managing, and/or preventing systemic lupus erythematosus (SLE). Pharmaceutical compositions and dosing regimens for use in the methods are also provided herein.

1 . A method for treating, preventing or managing systemic lupus erythematosus (SLE) comprising administering to a patient in need thereof an effective amount of a compound, which is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione of the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the compound is administered at an amount of about 0.6 mg per day. 
       
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. 
     
     
         4 . The method of  claim 1 , wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride. 
     
     
         5 . The method of  claim 1 , wherein the SLE is skin predominant SLE. 
     
     
         6 . A method for reducing, inhibiting or preventing a symptom of systemic lupus erythematosus (SLE), comprising administering to a patient having the symptom of systemic lupus erythematosus an effective amount of a compound, wherein the symptom is selected from the group consisting of joint pain, joint swelling, arthritis, chest pain when taking a deep breath, fatigue, fever with no other cause, general discomfort, uneasiness, hair loss, mouth sores, swollen lymph nodes, sensitivity to sunlight, skin rash, headaches, numbness, tingling, seizures, vision problems, personality changes, abdominal pain, nausea, vomiting, abnormal heart rhythms, coughing up blood and difficulty breathing, patchy skin color and Raynaud's phenomenon, and wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione of the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the compound is administered at an amount of about 0.6 mg per day. 
       
     
     
         7 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein administration of the compound continues for a period of from about 2 weeks to about 16 weeks. 
     
     
         13 . The method of  claim 1 , wherein administration of the compound continues for a period of about 28 days. 
     
     
         14 . The method of  claim 1 , wherein administration of the compound continues for a period of about 56 days. 
     
     
         15 . The method of claim  claim 1 , wherein administration of the compound continues for a period of about 84 days. 
     
     
         16 . The method of  claim 1 , wherein the compound is administered orally. 
     
     
         17 . The method of  claim 16 , wherein the compound is administered in a capsule. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 16 , wherein the compound is administered in a tablet. 
     
     
         20 . A method for identifying a subject having systemic lupus erythematosus (SLE) who is likely to be responsive to a treatment with a compound of formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof, comprising:
 (a) determining the level of a biomarker in a first sample from the subject, wherein the biomarker is selected from the group consisting of CRBN, IKZF1 (Ikaros), and IKZF3 (Aiolos); and 
 (b) comparing the level of the biomarker in the first sample to a reference level of the biomarker; wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the first sample is higher than the reference level of the biomarker. 
 
       
     
     
         21 - 61 . (canceled) 
     
     
         62 . The method of  claim 1 , wherein the SLE is severe SLE. 
     
     
         63 . The method of  claim 1 , wherein the patient has Cutaneous Lupus Area and Severity Index (CLASI) Activity Score ≥10. 
     
     
         64 . The method of  claim 6 , wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. 
     
     
         65 . The method of  claim 6 , wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride.