METHODS FOR TREATING PROGRESSIVE MULTIPLE SCLEROSIS

• US 20100158903A1
• Filed: 09/16/2009
• Published: 06/24/2010
• Est. Priority Date: 09/16/2008
• Status: Abandoned Application

• Current Assignee: F Hoffmann-La Roche AG (Roche Holding AG)
• Original Assignee: F Hoffmann-La Roche AG (Roche Holding AG)
• Inventors: Smith, Craig, Chin, Peter S.
• Application Number:
  US12/561,131
• Publication Number:
  US 20100158903A1
• Time in Patent Office: Days
• US Class Current: 424/133.100
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/7095 : Inflammation
• CPC Class Codes: G01N 33/686 : Anti-idiotype
• CPC Class Codes: G06Q 99/00 : Subject matter not provided for in other groups of this subclass

Abstract

The present invention concerns methods for treating progressive multiple sclerosis (MS) in a patient, and an article of manufacture with instructions for such use.

Claims

1. A method of treating progressive multiple sclerosis in a patient comprising administering to the patient an effective amount of an anti-CD20 antibody, wherein treatment is based upon the patient having one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points.

2. The method of claim 1, wherein the progressive multiple sclerosis is primary progressive multiple sclerosis.

3. The method of claim 1, wherein the progressive multiple sclerosis is secondary progressive multiple sclerosis.

4. The method of claim 1, wherein the progressive multiple sclerosis is progressive relapsing multiple sclerosis.

5. The method of claim 1, wherein the patient is not diagnosed with relapsing remitting multiple sclerosis when starting treatment.

6. The method of claim 1, wherein the patient further has evidence of inflammation in a sample.

7. The method of claim 6, wherein the sample is a cerebrospinal fluid sample.

8. The method of claim 7, wherein evidence of inflammation is indicated by an elevated IgG index.

9. The method of claim 7, wherein evidence of inflammation is indicated by IgG oligoclonal bands detected by isoelectric focusing.

10. The method of claim 1, wherein the patient has had an EDSS of greater than about 5.0 for less than about 15 years.

11. The method of claim 1, wherein the patient has had an EDSS less than or equal to about 5.0 for less than about 10 years.

12. The method of claim 1, wherein the increase in EDSS over two years prior to starting treatment is not attributable to relapse.

13. The method of claim 1, wherein the increase in EDSS is at least about a 1.5 point increase in EDSS over two years prior to starting treatment.

14. The method of claim 13, wherein the increase in EDSS over two years prior to starting treatment is not attributable to relapse.

15. The method of claim 1, wherein the age of the patient is less than about 51.

16. The method of claim 1, wherein the patient further had two or more relapses within two years prior to starting treatment.

17. The method of claim 1, wherein the EDSS when starting treatment is between about 3.0 and about 6.5.

18. The method of claim 1, wherein the treatment reduces the time to confirmed disease progression.

19. The method of claim 18, wherein confirmed disease progression is an increase in EDSS that is sustained for twelve weeks.

20. The method of claim 18, wherein confirmed disease progression is an increase in EDSS that is sustained for twenty-four weeks.

21. The method of claim 1, wherein the anti-CD20 antibody comprises:

a) a heavy chain variable region comprising three CDR regions comprising SEQ ID NO;

10, SEQ ID NO;

11, and SEQ ID NO;

12, and b) a light chain variable region comprising three CDR regions comprising SEQ ID NO;

4, SEQ ID NO;

5, and SEQ ID NO;

6.

22. The method of claim 1, wherein the anti-CD20 antibody is ocrelizumab.

23. The method of claim 1, wherein the anti-CD20 antibody is rituximab.

24. The method of claim 1, wherein the anti-CD20 antibody is ofatumumab.

25. The method of claim 1, wherein the anti-CD20 antibody is TRU-015 or SBI-087.

26. The method of claim 1, wherein the anti-CD20 antibody is GA101.

27. The method of claim 1, wherein the anti-CD20 antibody is hA20.

28. The method of claim 1, wherein the effective amount of the anti-CD20 antibody is administered to the patient to provide an initial anti-CD20 antibody exposure of between about 0.3 to about 4.0 grams followed by a second anti-CD20 antibody exposure of between about 0.3 to about 4.0 grams.

29. The method of claim 28, wherein the initial anti-CD20 antibody exposure and/or the second anti-CD20 antibody exposure is between about 0.3 to about 1.5 grams.

30. The method of claim 29, wherein the second exposure not being provided until from about 16 to 60 weeks from the initial exposure.

31. The method of claim 30, wherein each of the anti-CD20 antibody exposures is provided to the patient as one or two doses of anti-CD20 antibody.

32. A method of treating progressive multiple sclerosis in a patient provided that the patient has been found to have one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points, the treatment comprising administering to the patient an effective amount of an anti-CD20 antibody.

33. A method of treating progressive multiple sclerosis, comprising:

(a) selecting a patient having progressive multiple sclerosis, wherein said patient has one or more characteristics selected from the group consisting of (i) an age less than about 55 years, (ii) one or more gadolinium staining lesions, (iii) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (iv) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points; and

(b) administering to the patient thus selected an effective amount of an anti-CD20 antibody.

34. A method of assessing whether a patient with progressive multiple sclerosis will respond to treatment with an anti-CD20 antibody comprising assessing one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points, wherein one or more of the characteristics in the patient indicates the patient will be responsive to the treatment.

35. A method of identifying a patient with progressive multiple sclerosis likely to respond to anti-CD20 antibody treatment comprising:

(a) assessing one or more characteristics selected from the group consisting of (i) an age less than about 55 years, (ii) one or more gadolinium staining lesions, (iii) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (iv) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points; and

(b) identifying the patient having one or more characteristics selected from the group consisting of (i) an age less than about 55 years, (i) one or more gadolinium staining lesions, (iii) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting the anti-CD20 treatment, and (iv) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points.

36. A method for marketing an anti-CD20 antibody or a pharmaceutically acceptable composition thereof for use in a progressive multiple sclerosis patient subpopulation, the method comprising informing a target audience about the use of the anti-CD20 antibody for treating the patient subpopulation characterized by the patients of such subpopulation having one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points.

37. An article of manufacture comprising, packaged together, a pharmaceutical composition comprising an anti-CD20 antibody and a pharmaceutically acceptable carrier and a label denoting that the anti-CD20 antibody or pharmaceutical composition is indicated for treating patients with multiple sclerosis having one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points.

38. A method for predicting whether a subject with progressive multiple sclerosis will respond to a treatment with a drug used to treat multiple sclerosis, the method comprising assessing one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points, whereby the age, the gadolinium staining lesions, the increase in EDDS over two years prior to starting the treatment, or a combination thereof indicates that the subject will respond to the treatment.

39. A method of treating multiple sclerosis in a patient comprising administering an effective amount of ocrelizumab to the patient to provide an initial ocrelizumab exposure of between about 0.3 to about 0.6 grams followed by a second ocrelizumab exposure of between about 0.3 to about 0.6 grams, the second exposure not being provided until from about 16 to 60 weeks from the initial exposure, and each of the ocrelizumab exposures is provided to the patient as one or two doses of ocrelizumab.

40. The method of claim 39, wherein the initial ocrelizumab exposure comprises a first dose and a second dose of ocrelizumab, wherein the first dose and second dose of ocrelizumab is about 0.3 grams.

41. The method of claim 40, wherein the second ocrelizumab exposure comprises a single dose of ocrelizumab, wherein the single dose of ocrelizumab is 0.6 grams.

42. The method of claim 41, wherein the second ocrelizumab exposure is provided approximately 24 weeks after the initial ocrelizumab exposure.

43. The method of claim 42, further comprising providing a third ocrelizumab exposure.

44. The method of claim 43, further comprising providing a fourth ocrelizumab exposure.

45. The method of claim 44, further comprising providing a fifth ocrelizumab exposure.

46. The method of claim 42, further comprising providing between about one to about three subsequent ocrelizumab exposures.

47. An article of manufacture comprising:

(a) a container comprising ocrelizumab; and

(b) a package insert with instructions for treating multiple sclerosis in a patient, wherein the instructions indicate that an amount of ocrelizumab is administered to the patient that is effective to provide an initial ocrelizumab exposure of between about 0.3 to about 0.6 grams followed by a second ocrelizumab exposure of between about 0.3 to about 0.6 grams, the second exposure not being administered until from about 16 to 60 weeks from the initial exposure, and each of the ocrelizumab exposures is provided to the patient as one or two doses of ocrelizumab.