TREATMENT OF JAK2-MEDIATED CONDITIONS
Described herein is a method for treating a subject experiencing anemia, comprising administering to the subject an amount of N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide [CYT387 ] or a related compound effective to maintain or elevate the hemoglobin level. The anemic subjects including those afflicted with a myeloproliferative disorder, such as primary myelofibrosis.
1 . A method for treating a subject experiencing anemia, comprising administering to the subject an amount of N-(cyanomethyl)-4-[ 2 -[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide [CYT387 ] or a related compound effective to maintain or elevate the hemoglobin level.
2 . The method according to claim 1 , wherein the subject experiencing anemia is afflicted with a myeloproliferative disorder.
3 . The method according to claim 2 , wherein the subject experiencing anemia is afflicted with primary myelofibrosis.
4 . The method according to claim 3 , wherein the subject experiencing anemia is afflicted with primary myelofibrosis secondary to polycythemia vera.
5 . The method according to claim 3 , wherein the subject experiencing anemia is afflicted with primary myelofibrosis secondary to essential thrombocythemia.
6 . The method according to claim 2 , wherein the subject experiencing anemia is afflicted with myelodisplastic syndrome.
7 . The method according to any one of claims 1 - 6 , wherein the compound is CYT387.
8 . The method according to claim 7 , wherein the compound is the dihydrochloride salt of CYT387.
9 . The method according to any one of claims 1 - 8 , wherein the anemic subject is not afflicted with a myeloproliferative disorder.
10 . The use of CYT387 to treat anemia.
11 . An article of manufacture, comprising a container comprising CYT387 in an amount useful to treat anemia and, associated with said container, a label indicating treatment of a subject afflicted with anemia.
12 . A kit comprising a container comprising CYT387 in an amount useful to treat anemia and, in association therewith, printed instruction teaching a method for said treatment.
13 . An improved method for treating a subject having, or at risk for, a medical condition for which a JAK inhibitor is indicated, the method comprising the steps of (1) selecting, for treatment, a subject that meets at least one of the following criteria:
(i) prior therapy with a drug selected from thalidomide, lenalidomide, pomalidomide and a JAK inhibitor other than CYT387;
(ii) a clinical criterion selected from one or both of (1) larger spleen size and (2) lower percentage of circulating blasts;
(iii) a biochemical marker criterion selected from one or more of (1) an increased level of at least one protein selected from EGF, TNF-α, G-CSF, IFN-α, MIP-1β, HGF, MIG, and VEGF; (2) a decreased level of eotaxin; and (3) an altered level of at least one protein selected from EPO, hepcidin and BMP-2;
and then (2) administering to the selected subject a treatment-effective amount of CYT387, whereby the treated subject exhibits an anemia response and/or a spleen response that is improved relative to a subject not meeting any of said criteria.
14 . The method according to claim 13 , wherein the indication for which the JAK inhibitor is indicated is a myeloproliferative neoplasm.
15 . The method according to claim 14 , wherein the myeloproliferative neoplasm is primary myelofibrosis.
16 . The method according to claim 13 , wherein the myeloproliferative neoplasm is primary myelofibrosis secondary to polycythemia vera.
17 . The method according to claim 13 , wherein the myeloproliferative neoplasm is primary myelofibrosis secondary to essential thrombocythemia.
18 . The method according to claims 13 - 17 , comprising the preliminary step of screening said subject or a biological sample obtained therefrom to assess at least one of said criteria.
19 . The method according to claim 18 , wherein a biological sample obtained from said subject is screened to assess the level of at least one of said biochemical markers.
20 . An article of manufacture, comprising container comprising CYT387 in an amount useful to treat MPN and, associated with said container, a label indicating treatment of a subject identified according to claim 13 .
21 . A kit comprising a container comprising CYT387 in an amount useful to treat MPN and, in association therewith, printed instruction teaching a method according to claim 13 .