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US 2026/0294956 A1Published application
Treatment of hemophilia with fitusiran
AssigneeGenzyme Corporation
InventorsMalidi AHAMADI, Timothy CHOW, Marek DEMISSIE, Erica FERRARI, Dirk HOERTER, Laurel MENAPACE, Marja PUURUNEN
Life of this patent
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Abstract
The present disclosure provides methods for using fitusiran to treat patients with hemophilia A or hemophilia B.
Claims24
A method of routine prophylaxis to prevent or reduce the frequency of bleeding episodes in a human patient having hemophilia A or B with or without factor VIII or factor IX inhibitors, comprising:
- (a) subcutaneously administering to the human patient in need thereof fitusiran at a starting dose of 50 mg about once every 2 months;
- (b) obtaining a measurement of an antithrombin (AT) level in the human patient;
- (c) performing one of the following steps:
- (i) if the AT level is 15-35%, repeating step (a),
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months;
- (d) after administering to the human patient fitusiran at a dose of 20 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- (e) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months;
- (f) after administering to the human patient fitusiran at a dose of 10 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- and
- (g) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every month, or
- (iii) if the AT level is <15%, discontinuing or pausing fitusiran treatment.
14 more elements
A method of reducing a risk of hepatotoxicity in a human patient with hemophilia A or B with or without factor VIII or factor IX inhibitors who receives fitusiran for routine prophylaxis to prevent or reduce the frequency of bleeding episodes, comprising:
- (a) obtaining a measurement of an antithrombin (AT) level in the human patient, wherein the human patient has previously received fitusiran at a starting dose of 50 mg about once every 2 months;
- (b) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months;
- (c) after administering to the human patient fitusiran at a dose of 20 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- (d) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months;
- (e) after administering to the human patient fitusiran at a dose of 10 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- and
- (f) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every month, or
- (iii) if the AT level is <15%, discontinuing or pausing fitusiran treatment.
13 more elements
A method of reducing a risk of gallbladder disease in a human patient with hemophilia A or B with or without factor VIII or factor IX inhibitors who receives fitusiran for routine prophylaxis to prevent or reduce the frequency of bleeding episodes, comprising:
- (a) obtaining a measurement of an antithrombin (AT) level in the human patient, wherein the human patient has previously received fitusiran at a starting dose of 50 mg about once every 2 months;
- (b) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months;
- (c) after administering to the human patient fitusiran at a dose of 20 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- (d) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months;
- (e) after administering to the human patient fitusiran at a dose of 10 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- and
- (f) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every month, or
- (iii) if the AT level is <15%, discontinuing or pausing fitusiran treatment.
13 more elements
A method of reducing thrombotic risk in a human patient with hemophilia A or B with or without factor VIII or factor IX inhibitors who receives fitusiran for routine prophylaxis to prevent or reduce the frequency of bleeding episodes, comprising:
- (a) obtaining a measurement of an antithrombin (AT) level in the human patient, wherein the human patient has previously received fitusiran at a starting dose of 50 mg about once every 2 months;
- (b) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months;
- (c) after administering to the human patient fitusiran at a dose of 20 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- (d) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months;
- (e) after administering to the human patient fitusiran at a dose of 10 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- and
- (f) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every month, or
- (iii) if the AT level is <15%, discontinuing or pausing fitusiran treatment.
13 more elements
A method of monitoring an antithrombin level in a human patient with hemophilia A or B with or without factor VIII or factor IX inhibitors who receives fitusiran for routine prophylaxis to prevent or reduce the frequency of bleeding episodes, comprising:
- (a) obtaining a measurement of an antithrombin (AT) level in the human patient, wherein the human patient has previously received fitusiran at a starting dose of 50 mg about once every 2 months;
- (b) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months;
- (c) after administering to the human patient fitusiran at a dose of 20 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- (d) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months;
- (e) after administering to the human patient fitusiran at a dose of 10 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- and
- (f) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every month, or
- (iii) if the AT level is <15%, discontinuing or pausing fitusiran treatment.
13 more elements
A method of reducing annualized bleeding rate in a human patient with hemophilia A or B with or without factor VIII or factor IX inhibitors who receives fitusiran for routine prophylaxis to prevent or reduce the frequency of bleeding episodes, comprising:
- (a) obtaining a measurement of an antithrombin (AT) level in the human patient, wherein the human patient has previously received fitusiran at a starting dose of 50 mg about once every 2 months;
- (b) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 50 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months;
- (c) after administering to the human patient fitusiran at a dose of 20 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- (d) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 20 mg about once every month, or
- (iii) if the AT level is <15%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months;
- (e) after administering to the human patient fitusiran at a dose of 10 mg about once every 2 months, obtaining a measurement of an antithrombin (AT) level in the human patient;
- and
- (f) performing one of the following steps:
- (i) if the AT level is 15-35%, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every 2 months,
- (ii) if the AT level is >35% after 6 months, subcutaneously administering to the human patient fitusiran at a dose of 10 mg about once every month, or
- (iii) if the AT level is <15%, discontinuing or pausing fitusiran treatment.
13 more elements
A pharmaceutical composition, comprising fitusiran at a concentration of about 35 mg/ml to about 45 mg/mL and phosphate buffered saline (PBS) at a concentration of about 1 mM to about 10 mM,
- wherein the pH and the osmolality of the pharmaceutical composition are suitable for subcutaneous administration to a subject, and
- wherein the composition comprises about 7.67 to about 7.69 mg/mL sodium chloride, about 0.932 to about 0.934 mg/mL dibasic sodium phosphate (heptahydrate), and about 0.208 to about 0.211 mg/mL monobasic sodium phosphate (monohydrate), wherein the pH of the composition is between about 5.0 to about 8.0.
A pharmaceutical composition comprising fitusiran, wherein:
- (a) 0.5 mL of the pharmaceutical composition comprises about 50 mg of fitusiran (equivalent to about 53.0 mg fitusiran sodium), about 0.585 mg dibasic sodium phosphate, about 0.044 mg monobasic sodium phosphate, about 2.455 mg sodium chloride, and water for injection, wherein the pH of the pharmaceutical composition is about 7.0;
- (b) 0.5 mL of the pharmaceutical composition comprises about 20 mg of fitusiran (equivalent to about 21.2 mg fitusiran sodium), about 0.467 mg dibasic sodium phosphate, about 0.105 mg monobasic sodium phosphate, about 3.836 mg sodium chloride, and water for injection, wherein the pH of the pharmaceutical composition is about 7.0;
- or
- (c) 0.2 mL of the pharmaceutical composition comprises about 20 mg of fitusiran (equivalent to about 21.2 mg fitusiran sodium), about 0.234 mg dibasic sodium phosphate, about 0.018 mg monobasic sodium phosphate, about 0.982 mg sodium chloride, and water for injection.
1 more element
Dependencies are inferred from the claim text.