DENOSUMAB FORMULATION
An aqueous pharmaceutical formulation having improved stability includes denosumab and a poloxamer, and preferably a histidine buffer and/or sugar or sugar alcohol. The formulation is for use in treating or preventing osteoporosis, loss of bone mass, skeletal-related events associated with multiple myeloma, solid tumor bone metastases, giant cell tumors of the bone or hypercalcemia.
1 . An aqueous pharmaceutical formulation, comprising denosumab and a poloxamer.
2 . The aqueous formulation as claimed in claim 1 , comprising about 50 to about 80 mg/mL denosumab.
3 . The aqueous formulation as claimed in claim 1 , wherein the poloxamer is poloxamer 188.
4 . The aqueous formulation as claimed in claim 1 , comprising about 0.005 to about 0.1% (w/v) poloxamer.
5 . The aqueous formulation as claimed in claim 1 , further comprising a histidine buffer.
6 . The aqueous formulation as claimed in claim 1 , further comprising a sugar or sugar alcohol in an amount of about 200 to about 300 mM.
7 . The aqueous formulation as claimed in claim 1 , having a pH of about 5.5 to about 6.5.
8 . The aqueous formulation as claimed in claim 1 , comprising:
about 60 or about 70 mg/mL denosumab;
about 240 mM sucrose;
about 5 mM histidine buffer;
about 0.03% (w/v) poloxamer 188;
water; and
wherein the formulation has a pH of about 6.2.
9 . The aqueous formulation as claimed in claim 1 , formulated for parenteral injection.
10 . The aqueous formulation as claimed claim 1 , wherein the formulation exhibits a loss of surfactant concentration of 40% or less, when stored for one month at 25° C.
11 . The aqueous formulation as claimed in claim 1 , wherein the formulation exhibits a loss of surfactant concentration of 50% or less, when stored for one month at 40° C.
12 . A method for treating at least one selected from the group consisting of osteoporosis, loss of bone mass, skeletal-related events associated with multiple myeloma, solid tumor bone metastases, giant cell tumors of the bone, and hypercalcemia comprising administering the aqueous formulation as claimed in of claim 1 to a subject in need of such treatment.