Fitusiran for the treatment of hemophilia a and b in pediatric patients
AssigneeGenzyme Corporation
InventorsShauna ANDERSSON, Pratik R BHAGUNDE, Sajida IQBAL, Pranav PATEL, Stacey POLOSKEY, Fadi SHAMMAS
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods and compositions for treating pediatric patients with hemophilia A or B with or without inhibitors.
Claims51
A method of prophylactic treatment of hemophilia A or B in a pediatric patient with or without inhibitors, comprising:
- (a) subcutaneously administering to the patient in need thereof fitusiran at a starting dose amount at a selected dosing frequency;
- (b) obtaining a measurement of an antithrombin (AT) level in the patient;
- and
- (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%, subcutaneously administering to the patient fitusiran at a higher dose amount at the selected dosing frequency or at the starting dose amount at a higher dosing frequency, or
- (iii) if the AT level is <15%, subcutaneously administering to the patient fitusiran at a lower dose amount at the selected dosing frequency or at the starting dose amount at a lower dosing frequency, optionally wherein step (c) (iii) is performed after a pause in fitusiran administration and after the AT level in the patient has returned to ≥15%, optionally ≥22%.
A method of reducing thrombotic risk in a pediatric patient receiving fitusiran for prophylactic treatment of hemophilia A or B with or without inhibitors, comprising:
- (a) subcutaneously administering to the patient in need thereof fitusiran at a starting dose amount at a selected dosing frequency;
- (b) obtaining a measurement of an antithrombin (AT) level in the patient;
- and
- (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%, subcutaneously administering to the patient fitusiran at a higher dose amount at the selected dosing frequency or at the starting dose amount at a higher dosing frequency, or
- (iii) if the AT level is <15%, subcutaneously administering to the patient fitusiran at a lower dose amount at the selected dosing frequency or at the starting dose amount at a lower dosing frequency, optionally wherein step (c) (iii) is performed after a pause in fitusiran administration and after the AT level in the patient has returned to ≥15%, optionally ≥22%.
A method of reducing the frequency of bleeding episodes in a pediatric patient with hemophilia A or B with or without inhibitors, comprising:
- (a) subcutaneously administering to the patient in need thereof fitusiran at a starting dose amount at a selected dosing frequency;
- (b) obtaining a measurement of an antithrombin (AT) level in the patient;
- and
- (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%, subcutaneously administering to the patient fitusiran at a higher dose amount at the selected dosing frequency or at the starting dose amount at a higher dosing frequency, or
- (iii) if the AT level is <15%, subcutaneously administering to the patient fitusiran at a lower dose amount at the selected dosing frequency or at the starting dose amount at a lower dosing frequency, optionally wherein step (c) (iii) is performed after a pause in fitusiran administration and after the AT level in the patient has returned to ≥15%, optionally ≥22%.
A method of reducing the annual bleeding rate (ABR), the annual spontaneous bleeding rate (AsBR), and/or the annual joint bleeding rate (AjBR) in a pediatric patient with hemophilia A or B with or without inhibitors, comprising:
- (a) subcutaneously administering to the patient in need thereof fitusiran at a starting dose amount at a selected dosing frequency;
- (b) obtaining a measurement of an antithrombin (AT) level in the patient;
- and
- (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%, subcutaneously administering to the patient fitusiran at a higher dose amount at the selected dosing frequency or at the starting dose amount at a higher dosing frequency, or
- (iii) if the AT level is <15%, subcutaneously administering to the patient fitusiran at a lower dose amount at the selected dosing frequency or at the starting dose amount at a lower dosing frequency, optionally wherein step (c) (iii) is performed after a pause in fitusiran administration and after the AT level in the patient has returned to >15%, optionally ≥22%.
The method of any one of the preceding claims, further comprising subcutaneously administering fitusiran to the patient at a dose amount and a dosing frequency sufficient to maintain the AT level in the patient at 15-35%, optionally comprising subcutaneously administering fitusiran at:
- 1.25 mg QM or Q4W,
- 2.5 mg QM or Q4W,
- 5 mg QM or Q4W,
- 7.5 mg QM or Q4W,
- 10 mg QM or Q4W,
- 20 mg QM or Q4W,
- 30 mg QM or Q4W, or
- 50 mg QM or Q4W.
The method of any one of the preceding claims, wherein each AT level measurement is obtained after the patient has received at least two doses of fitusiran at a given dose amount.
The method of any one of the preceding claims, further comprising:
- (d) after step (c), if the patient has an AT level of 15-35% and has at least two doses of fitusiran at the step (c) dose amount and has two or more treated bleeds within a 12-week period starting with the third fitusiran injection at the step (c) dose amount, subcutaneously administering to the patient a higher dose amount of fitusiran than the step (c) dose amount.
The method of any one of the preceding claims, wherein the patient continues a previous non-fitusiran prophylactic treatment for just one week after the first dose of fitusiran, optionally wherein the previous non-fitusiran prophylactic treatment is a replacement factor treatment or a bypassing agent treatment.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 1.25 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 2.5 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 5 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 7.5 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 10 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 20 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 30 mg of fitusiran every month or every four weeks.
A method of prophylactic treatment of hemophilia A or B in a patient with or without inhibitors, or reducing the frequency of bleeding episodes, optionally the ABR, the AsBR, or the AjBR, in the patient, comprising subcutaneously administering to the patient in need thereof 50 mg of fitusiran every month or every four weeks.
The method of any one of the preceding claims, comprising obtaining a measurement of AT level in the patient every four weeks, every eight weeks, every month, every two months, every four months, every six months, or every 12 months.
The method of any one of the preceding claims, wherein fitusiran is provided in a phosphate-buffered saline (PBS) at 1-200 mg/mL, optionally 6.25 mg/mL, 12.5 mg/mL or 100 mg/mL.
An aqueous fitusiran composition comprising:
- 12.5 mg/mL fitusiran,
- 0.388 mg/mL NaH2PO4*H2O,
- 0.586 mg/mL Na2HPO4*7H2O, and
- 8.7 mg/mL NaCl,
- with a pH of about 7.0-7.1.
Dependencies are inferred from the claim text.