Methods for treating lower risk myelodysplastic syndrome

Abstract

The present disclosure relates to the use of pelabresib, and pharmaceutically acceptable salts and hydrates thereof, for treating lower risk myelodysplastic syndrome (LR-MDS) and conditions associated therewith.

Description

This invention relates to the use of perapusesiba and its pharmaceutically acceptable salts and hydrates for the treatment of low-risk myelodysplastic syndromes (LR-MDS) and related conditions. Abstract

Claims

Listing of Claims:

1. A method of treating lower-risk myelodysplastic syndrome (LR-MDS) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of pelabresib, or a pharmaceutically acceptable salt thereof.

2. The method of Claim 1, wherein the subject is administered a therapeutically effective amount of pelabresib.

3. The method of Claim 1 or 2, wherein the pelabresib is a hydrate.

4. The method of Claim 1 or 3, wherein the pelabresib is a monohydrate.

5. The method of any one of Claims 1 to 4, wherein the pelabresib is in crystalline form.

6. The method of any one of Claims 1 to 5, wherein the pelabresib is crystalline Form A characterized by at least three, at least four, at least five, or by six x-ray powder diffraction peaks at 20 angles selected from 4.73°, 18.09°, 18.48°, 18.80°, 19.70°, and 25.17°.

7. The method of any one of Claims 1 to 6, wherein the pelabresib is crystalline Form A characterized by at least three x-ray powder diffraction peaks at 20 angles selected from 4.73°, 18.09°, 18.48°, 18.80°, 19.70°, and 25.17°.

8. The method of any one of Claims 1 to 7, wherein the pelabresib is crystalline Form A characterized by at least four x-ray powder diffraction peaks at 20 angles selected from 4.73°, 18.09°, 18.48°, 18.80°, 19.70°, and 25.17°.

9. The method of any one of Claims 1 to 8, wherein the pelabresib is crystalline Form A characterized by at least five x-ray powder diffraction peaks at 20 angles selected from 4.73°, 18.09°, 18.48°, 18.80°, 19.70°, and 25.17°.

10. The method of any one of Claims 1 to 9, wherein the pelabresib is crystalline Form A characterized by a x-ray powder diffraction peaks at 20 angles selected from 4.73°, 18.09°, 18.48°, 18.80°, 19.70°, and 25.17°.

11. The method of any one of Claims 1 to 10, wherein the LR-MDS is low risk-MDS.

12. The method of any one of Claims 1 to 11, wherein the LR-MDS is very low risk-MDS13. The method of any one of Claims 1 to 12, wherein the subject is anemic.

14. The method of any one of Claims 1 to 13, wherein the subject is red blood cell transfusion dependent prior to treatment.

15. The method of Claim 14, wherein the subject becomes transfusion independent during treatment.

16. The method of Claim 14 or 15, wherein transfusion independent is characterized by the absence of a RBC transfusion for a period of about 8 consecutive weeks during treatment.

17. The method of Claim 15, wherein transfusion independent is characterized by the absence of a RBC transfusion during any consecutive 56-day period after the start of treatment.

18. The method of any one of Claims 1 to 17, wherein the subject experiences an improvement in hemoglobin levels during treatment.

19. The method of Claim 18, wherein the improvement in hemoglobin is characterized as an increase in hemoglobin levels of about >1.0 g / dL during treatment.

20. The method of any one of Claims 1 to 16, 18, and 19, wherein the subject becomes transfusion independent characterized by the absence of a RBC transfusion for a period of about 8 consecutive weeks during treatment and wherein the subject experiences an improvement in hemoglobin characterized as a mean hemoglobin increase of >1.0 g / dL during the transfusion independent period of about 8 consecutive weeks.

21. The method of any one of Claims 1 to 16, 18, and 19, wherein the subject becomes transfusion independent characterized by the absence of a RBC transfusion for a period of about 8 consecutive weeks during treatment and wherein the subject experiences an Erythroid Response (mHI-E) defined as an RBC transfusion reduction of >4 units during the transfusion independent period of about 8 consecutive weeks.

22. The method of any one of Claims 1 to 16, 18, and 19, wherein the subject becomes transfusion independent characterized by the absence of a RBC transfusion for a period of about 8 consecutive weeks during treatment and wherein the subject experiences an Erythroid Response (mHI-E) defined as a mean hemoglobin increase of >1.5 g / dL during the transfusion independent period of about 8 consecutive weeks.

23. The method of any one of Claims 1 to 22, wherein the subject experiences a Neutrophil Response (HI-N) during treatment.

24. The method of any one of Claims 1 to 23, wherein the subject experiences a Neutrophil Response (HI-N) during treatment characterized by a relative increase of >100% and an absolute increase of >0.5 x 109 / L from baseline in neutrophil count at every assessment during any consecutive 8-week period post baseline, for patients with baseline neutrophil count of <1.0 x 109 / L.

25. The method of any one of Claims 1 to 24, wherein the subject has a platelet count of > 75 x 109 / L prior to treatment.

26. The method of any one of Claims 1 to 24, wherein the subject has a platelet count of < 75 x 109 / L prior to treatment.

27. The method of any one of Claims 1 to 24, wherein the subject has a platelet count of > 50 x 109 / L < 75 x 109 / L prior to treatment.

28. The method of any one of Claims 1 to 27, wherein the subject experiences a Platelet Response (HI-P) during treatment.

29. The method of any one of Claims 1 to 24, wherein the subject has a baseline platelet count between 20 x 109 / L and 100 x 109 / L and experiences a Platelet Response (HI-P) during treatment characterized by an absolute increase of >30 x 109 / L from baseline, at every assessment during any consecutive 8-week period post baseline.

30. The method of any one of Claims 1 to 24, wherein the subject has a baseline platelet count of <20 x 109 / L and experiences a Platelet Response (HI-P) during treatment characterized by a relative increase of >100% from baseline, at every assessment during any consecutive 8-week period post baseline.

31. The method of any one of Claims 1 to 30, wherein the subject is administered about 75 mg / day pelabresib.

32. The method of Claim 31, wherein the subject has a baseline platelet count of < 75 x 109 / L prior to treatment33. The method of any one of Claims 1 to 30, wherein the subject is administered about 125 mg / day pelabresib.

34. The method of any one of Claims 1 to 30, wherein the subject is administered about 150 mg / day pelabresib.

35. The method of any one of Claims 31, 33, and 34, wherein the subject has a baseline platelet count of > 75 x 109 / L prior to treatment.

36. The method of any one of Claims 1 to 30, wherein the subject is administered about 175 mg / day pelabresib.

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