Methods of treating anemia using formoterol or a pharmaceutically acceptable salt thereof
The present invention provides methods of treating anemia in a patient in need thereof, comprising administering to the patient in need thereof an effective amount of formoterol or a pharmaceutically acceptable salt thereof (e.g., formoterol fumarate or arformoterol tartrate). The formoterol or a pharmaceutically acceptable salt thereof (e.g., formoterol fumarate or arformoterol tartrate) may be administered conjointly with an erythropoiesis-stimulating agent, optionally wherein the anemia is refractory to the erythropoiesis-stimulating agent. The present invention further provides methods of promoting differentiation of an erythroid progenitor cell toward a mature red blood cell in a patient in need thereof, comprising administering an effective amount of formoterol or a pharmaceutically acceptable salt thereof (e.g., formoterol fumarate or arformoterol tartrate). The formoterol or a pharmaceutically acceptable salt thereof (e.g., formoterol fumarate or arformoterol tartrate) may be administered conjointly with other FDA approved drugs such as luspatercept, lenalidomide, erythropoiesis-stimulating agents (ESAs), including but not limited to epoetin alfa or darbepoetin alfa, and/or a hypomethylating agent, such as azacitidine and/or decitabine.
1 . A method of treating anemia in a human subject, the method comprising administering to the human subject an effective amount of formoterol or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the anemia is selected from the group consisting of macrocytic anemia, hemolytic anemia, anemia caused by a ribosomopathy, anemia caused by insufficiency of serine/threonine-protein kinase RIOK 2 , anemia associated with chronic kidney disease (CKD), anemia caused by one or more mutations or deletions in human chromosome 5 or in an ortholog thereof, anemia caused by one or more mutations and deletions in human chromosome 5 or in an ortholog thereof, stress-induced anemia, Diamond Blackfan anemia, aplastic anemia, Schwachman-Diamond syndrome, an anemia associated with an inflammatory disease, anemia associated with rheumatoid arthritis, anemia associated with multiple sclerosis, anemia secondary to chemotherapy in cancer patients, and anemia associated with a bone marrow failure syndrome.
3 . The method of claim 1 , wherein the anemia is associated with a cancer, and wherein the cancer is an intestinal cancer or a hematologic malignancy selected from myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).
4 . The method of claim 3 , wherein the intestinal cancer is colorectal cancer.
5 . A method of promoting differentiation of an erythroid progenitor cell toward a mature red blood cell in a human subject, comprising administering to the human subject in need thereof an effective amount of formoterol or a pharmaceutically acceptable salt thereof.
6 . The method of claim 5 , wherein the human subject is suffering from anemia.
7 . The method of claim 6 , wherein the anemia is selected from the group consisting of macrocytic anemia, hemolytic anemia, anemia caused by a ribosomopathy, anemia caused by insufficiency of serine/threonine-protein kinase RIOK2, anemia associated with chronic kidney disease (CKD), anemia caused by one or more mutations or deletions in human chromosome 5 or in an ortholog thereof, anemia caused by one or more mutations and deletions in human chromosome 5 or in an ortholog thereof, stress-induced anemia, Diamond Blackfan anemia, aplastic anemia, Schwachman-Diamond syndrome, an anemia associated with an inflammatory disease, anemia associated with rheumatoid arthritis, anemia associated with multiple sclerosis, anemia secondary to chemotherapy in cancer patients, and anemia associated with a bone marrow failure syndrome.
8 . The method of claim 6 , wherein the anemia is associated with a cancer, and wherein the cancer is an intestinal cancer or a hematologic malignancy selected from a myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).
9 . The method of claim 8 , wherein the intestinal cancer is colorectal cancer.
10 . The method of claim 1 , further comprising administering to the human subject in need thereof an effective amount of an erythropoiesis-stimulating agent selected from erythropoietin, epoetin alfa, epoetin beta, epoetin omega, epoetin zeta, and darbepoetin alfa.
11 . A method of treating anemia in a human subject, the method comprising administering to the human subject an effective amount of formoterol or a pharmaceutically acceptable salt thereof conjointly with an erythropoiesis-stimulating agent, wherein the anemia is refractory to the erythropoiesis-stimulating agent.
12 . The method of claim 11 , wherein the anemia is selected from the group consisting of macrocytic anemia, hemolytic anemia, anemia caused by a ribosomopathy, anemia caused by insufficiency of serine/threonine-protein kinase RIOK2, anemia associated with chronic kidney disease (CKD), anemia caused by one or more mutations or deletions in human chromosome 5 or in an ortholog thereof, anemia caused by one or more mutations and deletions in human chromosome 5 or in an ortholog thereof, stress-induced anemia, Diamond Blackfan anemia, aplastic anemia, Schwachman-Diamond syndrome, an anemia associated with an inflammatory disease, anemia associated with rheumatoid arthritis, anemia associated with multiple sclerosis, anemia secondary to chemotherapy in cancer patients, and anemia associated with a bone marrow failure syndrome.
13 . The method of claim 11 , wherein the anemia is associated with a cancer, and wherein the cancer is an intestinal cancer or a hematologic malignancy selected from a myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).
14 . The method of claim 13 , wherein the intestinal cancer is colorectal cancer.
15 . The method of claim 11 , wherein the erythropoiesis-stimulating agent is erythropoietin, epoetin alfa, epoetin beta, epoetin omega, epoetin zeta, or darbepoetin alfa.
16 . The method of claim 1 , wherein formoterol or the pharmaceutically acceptable salt thereof is orally administered to the human subject.
17 . The method of claim 1 , wherein formoterol or the pharmaceutically acceptable salt thereof is formoterol fumarate.
18 . The method of claim 1 , wherein formoterol or the pharmaceutically acceptable salt thereof is arformoterol.
19 . The method of claim 18 , wherein the arformoterol is arformoterol tartrate.
20 . The method of claim 1 , wherein formoterol or the pharmaceutically acceptable salt thereof is administered conjointly with luspatercept, lenalidomide, an erythropoiesis-stimulating agent (ESA), wherein the erythropoiesis-stimulating agent is optionally epoetin alfa or darbepoetin alfa, a hypomethylating agent, wherein the hypomethylating agent is optionally azacitidine, decitabine, or azacitidine and decitabine, or any combination thereof.