Methods of treating al amyloidosis

A method of treating a patient having AL amyloidosis, comprising administering an effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105), wherein the patient has (a) Mayo Stage IV AL amyloidosis, (b) a 6 minute walk distance (6 MWD)≥30 meters and ≤550 meters, (c) a 6 MWD≥150 meters and EF>50%, (d) Mayo Stage IV and an EF>50%, (e) Mayo Stage IV and a 6 MWD≥30 meters and ≤550 meters, or (f) Mayo Stage IV and a 6 MWD≥150 meters and EF>50% and (g) the patient has not previously received or does not concomitantly receive daratumumab.

A method of treating a patient having Mayo Stage IV AL amyloidosis and having NYHA class III or NYHA class IV, the method comprising administering to the patient a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of reducing the risk of mortality in a patient having Mayo Stage IV AL amyloidosis and having NYHA class III or NYHA class IV, the method comprising administering to the patient a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of reducing the risk of hospitalization in a patient having Mayo Stage IV AL amyloidosis, the method comprising administering to the patient a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of increasing the number of days alive out of hospital (DAOH) in a patient Mayo Stage IV amyloidosis, the method comprising administering to the patient a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of reducing NTproBNP in a patient having Mayo Stage IV AL amyloidosis, the method comprising administering to the patient a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of improving cardiac response rate in a patient having Mayo Stage IV AL amyloidosis, the method comprising administering a therapeutically effective amount of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of improving a six minute walk test (6 MWT) in a patient having Mayo Stage IV AL amyloidosis, the method comprising administering a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of increasing a Kansas City Cardiomyopatthy Questionnaire (KCCQ) score in a patient having Mayo Stage IV AL amyloidosis, the method comprising administering a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of increasing Major Organ Deterioration Progression Free Survival in a patient having Mayo Class IV AL amyloidosis, the method comprising administering to the patient a therapeutically effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105) amount, wherein the patient has not previously received or does not concomitantly receive daratumumab.

The method of any of the preceding claims, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions of 2A4, 7D8 or 11-1F4, and a heavy chain variable region comprising three complementarity determining regions of 2A4, 7D8 or 11-1F4, respectively.

The method of any of the preceding claims, wherein the antibody is a humanized version of 2A4.

The method of any of the preceding claims, wherein the patient is newly diagnosed and AL amyloidosis treatment naïve.

A method of treating a patient with AL amyloidosis who has a demonstrated 6 minute walk distance (6 MWD) of ≥30 meters and ≤550 meters or a 6 MWD greater than or equal to 150 meters and an ejection fraction (EF) of more than 50%, comprising administering to the patient an effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105), wherein the patient has not previously received or does not concomitantly receive daratumumab.

A method of reducing the risk of mortality in a patient with AL amyloidosis by at least 45%, comprising administering to the patient an effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105), wherein the patient has Mayo Stage IV AL amyloidosis and/or has a demonstrated 6 minute walk distance (6 MWD)≥30 meters and ≤550 meters, or a 6 MWD of greater than or equal to 150 meters and an ejection fraction (EF) of more than 50%, or the patient has Mayo Stage IV AL amyloidosis and an EF of >50%, wherein the patient has not previously received or does not concomitantly receive daratumumab.

The method of 94, wherein the risk of cardiac mortality is reduced by at least about 62.2%.

The method of any of the preceding claims, wherein the patient exhibits improvement in the 36-Item Short Form Survey Physical Component Score (SF-36 PCS) or SF-36v2 following treatment with the antibody.

The method of any of the preceding claims, wherein the effective dosage of the antibody is administered from a pharmaceutical formulation comprising the antibody at a concentration within the range from about 1 mg/mL to about 100 mg/mL.

The method of any of the preceding claims, wherein the dosage is from about 0.5 mg/kg to about 30 mg/kg and the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly.

The method of any of the preceding claims, wherein the duration of the treatment is at least 9 months.

The method of any of the preceding claims, wherein the duration is effective to achieve or maintain at least about a 3 point increase from baseline in SF-36 PCS or SF-36v2.

The method of any of the preceding claims, wherein the antibody is a Fab, Fab′, F(ab′)2, F(ab)c, Dab, nanobody, or Fv.

The method of any of the preceding claims, wherein treatment results in a 20% relative reduction in hospitalization.

The method of any of the preceding claims, wherein treatment results in a 310% to 60% reduction in NTproBNP from a baseline.

The method of any of the preceding claims, wherein treatment results in a >60% reduction in NTproBNP from a baseline to a nadir NTproBNP>400 pg/mL.

The method of any of the preceding claims, wherein treatment results in a nadir NTproBNP<400 pg/mL.

The method of any of the preceding claims, wherein treatment results in at least a 5 point change to a 20 point change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.

The method of any of the preceding claims, wherein after treatment of 12 months results in at least a 33 meter improvement in the 6 MWT.

A method of improving a 6 minute walk distance (6 MWD) in a patient having AL amyloidosis, comprising administering to the patient an effective dosage of an antibody which competes for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin with 2A4 (ATCC Accession Number PTA-9662) or 7D8 (ATCC Accession Number PTA-9468), or competes for binding to kappa light chain immunoglobulin with 11-1F4 (ATCC Accession Number PTA-105), wherein the patient has not previously received or does not concomitantly receive daratumumab.