Pediatric dosage and administration of anti-c5 antibodies for treatment of complement disorders
AssigneeAlexion Pharmaceuticals, Inc.
InventorsStephan ORTIZ, Jonathan MONTELEONE
Life of this patent
Estimating the term…
Abstract
Provided are devices, systems, and methods for clinical treatment of complement disorders (e.g., paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome) in a pediatric human patient using subcutaneous delivery systems (e.g., on-body device and/or syringe) to administer an effective amount of a therapeutic anti-C5 antibody such as ravulizumab, or antigen-binding fragment thereof.
Claims105
An on-body delivery system (OBDS) configured for administration of an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising complementarity determining region (CDR) 1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, to treat atypical hemolytic uremic syndrome (aHUS) or paroxysmal nocturnal hemoglobinuria (PNH) in a pediatric human patient in need thereof, wherein the patient is complement inhibitor treatment-naïve or eculizumab-experienced, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- subcutaneously once per week at a dose of:
- (i) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (ii) 490 mg to a patient weighing ≥40 kg.
An OBDS configured for treating aHUS or PNH in a pediatric human patient in need thereof, wherein the OBDS comprises an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the patient is complement inhibitor treatment-naïve or eculizumab-experienced, and wherein the OBDS comprises means for subcutaneous administration of:
- (i) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (ii) 490 mg to a patient weighing ≥40 kg.
An OBDS configured for administration of an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, to treat aHUS or PNH in a pediatric human patient in need thereof, wherein the patient is ravulizumab-experienced, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- subcutaneously once per week at a dose of:
- (i) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (ii) 490 mg to a patient weighing ≥40 kg.
An OBDS configured for treating aHUS or PNH in a pediatric human patient in need thereof, wherein the OBDS comprises an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the patient is ravulizumab-experienced, and wherein the OBDS comprises means for subcutaneous administration of:
- (i) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (ii) 490 mg to a patient weighing ≥40 kg.
A needle syringe configured for administration of an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, to treat aHUS or PNH in a pediatric human patient in need thereof, wherein the patient is ≥10 to <20 kg of body weight and is complement inhibitor treatment-naïve, eculizumab-experienced, or ravulizumab-experienced, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- subcutaneously once per week at a dose of 150 mg.
A needle syringe configured for treating aHUS or PNH in a pediatric human patient in need thereof, wherein the needle syringe is configured for subcutaneous administration and comprises 150 mg of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the patient is ≥10 to <20 kg of body weight and is complement inhibitor treatment-naïve, eculizumab-experienced, or ravulizumab-experienced.
A method of treating a pediatric human patient with PNH or aHUS, wherein the patient is complement inhibitor treatment-naïve or eculizumab-experienced, the method comprising administering to the patient during an administration cycle an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- (a) intravenously once on Day 1 of the administration cycle at a dose of:
- (i) 600 mg to a patient weighing ≥10 to <20 kg;
- (ii) 900 mg to a patient weighing ≥20 to <30 kg;
- (iii) 1200 mg to a patient weighing ≥30 to <40 kg;
- (iv) 2400 mg to a patient weighing ≥40 to <60 kg;
- or
- (v) 2700 mg to a patient weighing ≥60 kg, and
- (b) subcutaneously on Day 15 of the administration cycle and every week thereafter at a dose of:
- (i) 150 mg to a patient weighing ≥10 to <20 kg;
- (ii) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (iii) 490 mg to a patient weighing ≥40 kg.
A method of treating a pediatric human patient with PNH or aHUS, wherein the patient is ravulizumab-experienced, the method comprising administering to the patient during an administration cycle an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- subcutaneously on Day 1 of the administration cycle and every week thereafter at a dose of:
- (i) 150 mg to a patient weighing ≥10 to <20 kg;
- (ii) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (iii) 490 mg to a patient weighing ≥40 kg.
A therapeutic anti-C5 antibody, or antigen-binding fragment thereof, for use in treatment of a pediatric human patient with PNH or aHUS, wherein the patient is complement inhibitor treatment-naïve or eculizumab-experienced, the treatment comprising administering to the patient during an administration cycle an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- (a) intravenously once on Day 1 of the administration cycle at a dose of:
- (i) 600 mg to a patient weighing ≥10 to <20 kg;
- (ii) 900 mg to a patient weighing ≥20 to <30 kg;
- (iii) 1200 mg to a patient weighing ≥30 to <40 kg;
- (iv) 2400 mg to a patient weighing ≥40 to <60 kg;
- or
- (v) 2700 mg to a patient weighting ≥60 kg, and
- (b) subcutaneously on Day 15 of the administration cycle and every week thereafter at a dose of:
- (i) 150 mg to a patient weighing ≥10 to <20 kg;
- (ii) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (iii) 490 mg to a patient weighing ≥40 kg.
Use of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, in the manufacture of a medicament for treating aHUS or PNH in a pediatric human patient in need thereof, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the patient is complement inhibitor treatment-naïve or eculizumab-experienced, and wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is formulated for administration by:
- (a) intravenously once on Day 1 of the administration cycle at a dose of:
- (i) 600 mg to a patient weighing ≥10 to <20 kg;
- (ii) 900 mg to a patient weighing ≥20 to <30 kg;
- (iii) 1200 mg to a patient weighing ≥30 to <40 kg;
- (iv) 2400 mg to a patient weighing ≥40 to <60 kg;
- or
- (v) 2700 mg to a patient weighting ≥60 kg, and
- (b) subcutaneously on Day 15 of the administration cycle and every week thereafter at a dose of:
- (i) 150 mg to a patient weighing ≥10 to <20 kg;
- (ii) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (iii) 490 mg to a patient weighing ≥40 kg.
A therapeutic anti-C5 antibody, or antigen-binding fragment thereof, for use in treatment of a pediatric human patient with PNH or aHUS, wherein the patient is ravulizumab-experienced, the treatment comprising administering to the patient during an administration cycle an effective amount of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is administered:
- subcutaneously on Day 1 of the administration cycle and every week thereafter at a dose of:
- (i) 150 mg to a patient weighing ≥10 to <20 kg;
- (ii) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (iii) 490 mg to a patient weighing ≥40 kg.
Use of a therapeutic anti-C5 antibody, or antigen-binding fragment thereof, in the manufacture of a medicament for treating aHUS or PNH in a pediatric human patient in need thereof, wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, comprises CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:
- 19, 18, and 3, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:
- 4, 5, and 6, respectively, wherein the patient is ravulizumab-experienced, and wherein the therapeutic anti-C5 antibody, or antigen-binding fragment thereof, is formulated for administration:
- subcutaneously on Day 1 of the administration cycle and every week thereafter at a dose of:
- (i) 150 mg to a patient weighing ≥10 to <20 kg;
- (ii) 245 mg to a patient weighing ≥20 to <40 kg;
- or
- (iii) 490 mg to a patient weighing ≥40 kg once per week.
Dependencies are inferred from the claim text.