Treatment and prevention methods for Alzheimer's disease

Abstract

This invention provides a method for reducing clinical functional decline in individuals with early-stage Alzheimer's disease. [Solution] A method of administering a composition comprising a therapeutically effective amount of at least one anti-Aβ protofibril antibody, wherein the at least one anti-Aβ protofibril antibody is BAN2401.

Claims

1. A composition comprising a therapeutically effective amount of anti-Aβ protofibril antibody for reducing clinical functional decline in subjects with early-stage Alzheimer's disease, The composition is administered to the subject at a dose of 10 mg / kg of the anti-Aβ protofibril antibody based on the subject's body weight, once every two weeks for a period sufficient to reduce clinical functional impairment. The aforementioned subjects are ApoE4 positive, The anti-Aβ protofibril antibody comprises a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 1 and a light chain variable region containing the amino acid sequence of SEQ ID NO:

2. composition.

2. The composition according to claim 1, wherein the subject having early-stage Alzheimer's disease has been diagnosed with mild to moderate cognitive impairment due to Alzheimer's disease, and / or has been diagnosed with mild Alzheimer's disease-type dementia.

3. The composition according to claim 1 or 2, wherein the anti-Aβ protofibril antibody comprises a heavy chain indicated by SEQ ID NO: 11 and a light chain indicated by SEQ ID NO:

12.

4. The composition according to any one of claims 1 to 3, wherein the composition is administered over a period of at least 18 months or at least 24 months.

5. The composition according to any one of claims 1 to 4, wherein the composition is administered without titration.

6. The composition according to any one of claims 1 to 5, wherein the composition comprises sodium chloride.

7. The composition according to any one of claims 1 to 6, wherein the composition is administered intravenously.

8. The composition according to any one of claims 1 to 7, to be used in combination with the administration of at least one maintenance therapy.

9. The composition according to claim 8, wherein the at least one maintenance therapy is administered after the composition has been administered for 18 months, after the composition has been administered for 24 months, or after the subject has become amyloid-negative.

10. The composition according to claim 8 or 9, wherein the at least one maintenance therapy comprises the anti-Aβ protofibril antibody.

11. The composition according to claim 10, wherein at least one maintenance therapy is administered subcutaneously.

12. The composition according to claim 11, wherein the at least one maintenance therapy is administered once a week.

13. The composition according to claim 10, wherein at least one maintenance therapy is administered intravenously.

14. The composition according to claim 13, wherein the at least one maintenance therapy is administered once every two weeks, once every four weeks, or once every month.

15. The composition according to claim 13 or 14, wherein the at least one maintenance therapy is administered at a dose of 10 mg / kg of the anti-Aβ protofibril antibody based on the body weight of the subject.

16. The composition according to any one of claims 1 to 15, wherein the clinical functional impairment is reduced by at least 26% compared to placebo when determined by ADAS-Cog 18 months after administration of the composition.

17. The composition according to any one of claims 1 to 16, wherein the clinical functional impairment is reduced by at least 84% compared to placebo when determined by ADAS-Cog 18 months after administration of the composition.

18. The composition according to any one of claims 1 to 17, wherein the clinical functional decline is reduced by at least 21% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

19. The composition according to any one of claims 1 to 18, wherein the clinical functional impairment is reduced by at least 25% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

20. The composition according to any one of claims 1 to 19, wherein the clinical functional decline is reduced by at least 27% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

21. The composition according to any one of claims 1 to 20, wherein the clinical functional decline is reduced by at least 60% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

22. The composition according to any one of claims 1 to 21, wherein the clinical functional decline is reduced by 25% to 60% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

23. The composition according to any one of claims 1 to 22, wherein the clinical functional decline is reduced by 25% to 50% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

24. The composition according to any one of claims 1 to 23, wherein the clinical functional impairment is reduced by at least 20% compared to placebo when determined by ADCOMS 18 months after administration of the composition.

25. The composition according to any one of claims 1 to 24, wherein the clinical functional impairment is reduced by at least 24% compared to placebo when determined by ADCOMS 18 months after administration of the composition.

26. The composition according to any one of claims 1 to 25, wherein the clinical functional impairment is reduced by at least 63% compared to placebo when determined by ADCOMS 18 months after administration of the composition.

27. ​​The composition according to any one of claims 1 to 26, wherein the subject is a homozygous carrier of the ApoE4 gene allele.

28. The composition according to any one of claims 1 to 26, wherein the subject is a heterozygous carrier of the ApoE4 gene allele.

29. The composition according to claim 28, wherein the clinical functional impairment is reduced by at least 23% compared to placebo when determined by ADAS-Cog 18 months after administration of the composition.

30. The composition according to claim 28, wherein the clinical functional decline is reduced by at least 30% compared to placebo when determined by CDR-SB 18 months after administration of the composition.

31. The composition according to claim 28, wherein the clinical functional impairment is reduced by at least 25% compared to placebo when determined by ADCOMS 18 months after administration of the composition.

32. The composition according to any one of claims 1 to 31, wherein the reduction in clinical functional impairment includes a reduction in brain amyloid levels determined by visual interpretation of amyloid PET images and expressed as a PET standard uptake ratio (SUVr value), and the mean change from the adjusted baseline of the PET SUVr value of the subject is at least -0.20, at least -0.25, or at least -0.

30.

33. The composition according to any one of claims 1 to 32, wherein administration of the composition results in a reduction of total tau, phosphotau and / or neurogranin levels in the cerebrospinal fluid, and / or an increase in Aβ1-42 levels in the cerebrospinal fluid.

34. The composition according to any one of claims 1 to 33, wherein no Alzheimer's disease treatment agent other than the anti-Aβ protofibril antibody is co-administered to the subject.

35. The composition according to any one of claims 1 to 34, wherein the subject is monitored for ARIA-E and ARIA-H, and if ARIA-E or ARIA-H is detected, treatment is continued or discontinued.

36. The composition according to claim 35, wherein the monitoring comprises evaluating the subject three months after administration of the composition.

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