Methods of treating psoriasis using il-17 antagonists

Abstract

The disclosure relates to novel regimens for treating psoriasis, which employ a therapeutically effective amount of an IL-17 antagonist, e.g., an IL-17 binding molecule, e.g., an IL-17 antibody, such as the secukinumab antibody, or an IL-17 receptor binding molecule, e.g., an IL-17 receptor antibody.

1 . A method of treating psoriasis, comprising subcutaneously administering to a patient in need thereof a dose of about 150 mg-about 300 mg of an IL-17 antibody every four weeks, wherein the IL-17 antibody comprises:
 i) an immunoglobulin variable heavy (V H ) domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin variable heavy (V L ) domain comprising the amino acid sequence set forth as SEQ ID NO:10;   ii) an immunoglobulin V H  domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin V L  domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or   iii) an immunoglobulin V H  domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin V L  domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6.   
     
     
         2 . The method of  claim 1 , wherein the dose of the IL-17 antibody is about 150 mg or about 300 mg. 
     
     
         3 . The method according to  claim 2 , wherein, prior to treatment with the IL-17 antibody, the patient has not been previously treated with a systemic agent for psoriasis. 
     
     
         4 . The method according to  claim 2 , wherein, prior to treatment with the IL-17 antibody, the patient has been previously treated with a systemic agent for psoriasis. 
     
     
         5 . The method according to  claim 4 , wherein the systemic agent is selected from the group consisting of methotrexate, cyclosporine, fumaric acid esters, acitretin, alefacept, adalimumab, efalizumab, etanercept, infliximab, golimumab and ustekinumab. 
     
     
         6 . The method according to  claim 5 , wherein the systemic agent is methotrexate. 
     
     
         7 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 300 mg. 
     
     
         8 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 150 mg. 
     
     
         9 . The method of  claim 2 , wherein the patient has plaque psoriasis. 
     
     
         10 . The method of  claim 9 , wherein the patient has moderate to severe plaque psoriasis. 
     
     
         11 . The method of  claim 2 , wherein the patient has palm psoriasis, sole psoriasis, face psoriasis, scalp psoriasis, genital psoriasis, or nail psoriasis. 
     
     
         12 . The method of  claim 10 , wherein the patient is an adult patient. 
     
     
         13 . The method of  claim 2 , wherein the IL-17 antibody is comprised in a pharmaceutical formulation, wherein said pharmaceutical formulation further comprises a buffer and a stabilizer. 
     
     
         14 . The method of  claim 13 , wherein the pharmaceutical formulation is in liquid form. 
     
     
         15 . The method of  claim 13 , wherein the pharmaceutical formulation is a lyophilisate for reconstitution with an aqueous carrier prior to administration to the patient. 
     
     
         16 . The method of  claim 13 , wherein the pharmaceutical formulation is contained within at least one pre-filled syringe, at least one vial, at least one injection pen, or at least one autoinjector. 
     
     
         17 . The method of  claim 13 , wherein the dose of the IL-17 antibody is about 300 mg, wherein the pharmaceutical formulation is contained within an autoinjector, wherein said autoinjector is contained within a kit, and wherein said kit further comprises instructions for use. 
     
     
         18 . The method of  claim 13 , wherein the dose of the IL-17 antibody is about 150 mg, wherein the pharmaceutical formulation is contained within a pre-filled syringe, an injection pen, or an autoinjector, which is contained within a kit, and wherein said kit further comprises instructions for use. 
     
     
         19 . The method of  claim 13 , wherein the IL-17 antibody is secukinumab. 
     
     
         20 . The method of  claim 2 , wherein the IL-17 antibody has a T max  of about 7-8 days. 
     
     
         21 . The method of  claim 2 , wherein the IL-17 antibody has an absolute bioavailablilty of about 60-about 80%. 
     
     
         22 . The method of  claim 2 , wherein the step of administering the IL-17 antibody every four weeks provides an average steady-state trough level of the IL-17 antibody between about 5 μg/ml-about 70 μg/ml. 
     
     
         23 . The method of  claim 22 , wherein the step of administering the IL-17 antibody every four weeks provides an average steady-state trough level of the IL-17 antibody between about 5 μg/ml-about 33 μg/ml. 
     
     
         24 . The method of  claim 22 , wherein the step of administering the IL-17 antibody every four weeks provides an average steady-state trough level of the IL-17 antibody between about 11 μg/ml-about 70 μg/ml. 
     
     
         25 . The method of  claim 2 , wherein the IL-17 antibody is a human monoclonal antibody. 
     
     
         26 . The method of  claim 25 , wherein the IL-17 antibody is of the IgG 1 /kappa isotype. 
     
     
         27 . The method according to  claim 10 , wherein, prior to treatment with the IL-17 antibody, the patient has an Investigator Global Assessment (IGA) score of ≥3. 
     
     
         28 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 300 mg and the patient weighs more than 90 kg. 
     
     
         29 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 300 mg and the patient weighs more than or equal to 90 kg. 
     
     
         30 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 300 mg and the patient weighs more than 100 kg. 
     
     
         31 . The method of  claim 28 , wherein the IL-17 antibody is secukinumab. 
     
     
         32 . The method of  claim 29 , wherein the IL-17 antibody is secukinumab. 
     
     
         33 . The method of  claim 30 , wherein the IL-17 antibody is secukinumab. 
     
     
         34 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 150 mg and the patient weighs less than 90 kg. 
     
     
         35 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 150 mg and the patient weighs less than or equal to 90 kg. 
     
     
         36 . The method of  claim 2 , wherein the dose of the IL-17 antibody is about 150 mg and the patient weighs less than or equal to 100 kg. 
     
     
         37 . A method of treating psoriasis, comprising subcutaneously administering to a patient in need thereof a dose of about 150 mg or about 300 mg secukinumab every four weeks, wherein the patient is a candidate for systemic therapy or phototherapy. 
     
     
         38 .- 40 . (canceled)