COMPOSITIONS CONTAINING AND THERAPIES USING BEMPEDOIC ACID AND TOLVAPTAN

1 . A fixed-dose combination comprising bempedoic acid and tolvaptan.

2 . The fixed-dose combination of claim 1 , wherein the fixed-dose combination comprises about 30 mg to about 240 mg bempedoic acid.

3 . The fixed-dose combination of claim 1 or 2 , wherein the fixed-dose combination comprises about 5 mg to about 120 mg tolvaptan, about 5 mg to about 90 mg tolvaptan, or about 5 mg to about 60 mg tolvaptan.

4 . The fixed-dose combination of any one of claims 1-3 , wherein the fixed-dose combination comprises about 5 mg, about 10 mg, about 15 mg, about 30 mg, about 45 mg, about 60 mg, or about 90 mg tolvaptan.

5 . The fixed-dose combination of any one of claims 1-4 , wherein the fixed-dose combination comprises about 180 mg bempedoic acid.

6 . A pharmaceutical composition comprising:

bempedoic acid;

tolvaptan; and

one or more pharmaceutically acceptable excipients.

7 . The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition comprises about 30 mg to about 240 mg bempedoic acid.

8 . The pharmaceutical composition of claim 6 or 7 , wherein the pharmaceutical composition comprises about 5 mg to about 120 mg tolvaptan, about 5 mg to about 90 mg tolvaptan, or about 5 mg to about 60 mg tolvaptan.

9 . The pharmaceutical composition of any one of claims 6-8 , wherein the pharmaceutical composition comprises about 5 mg, about 10 mg, about 15 mg, about 30 mg, about 45 mg, about 60 mg, or about 90 mg tolvaptan.

10 . The pharmaceutical composition of any one of claims 6-9 , wherein the pharmaceutical composition comprises about 180 mg bempedoic acid.

11 . The fixed-dose combination of any one of claims 1-5 or the pharmaceutical composition of any one of claim 6-10 , wherein the fixed-dose combination or the pharmaceutical composition is formulated for oral delivery.

12 . The fixed-dose combination or the pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is formulated as an oral solid dosage form selected from the group consisting of a tablet, a capsule, a softgel capsule, a pill, a solution, and a suspension.

13 . The fixed-dose combination of any one of claims 1-5, 11, and 12 , or the pharmaceutical composition of any one of claims 6-12 , wherein the fixed-dose combination or the pharmaceutical composition provides immediate release of bempedoic acid.

14 . The fixed-dose combination of any one of claims 1-5, 11, and 12 , or the pharmaceutical composition of any one of claims 6-12 , wherein the fixed-dose combination or the pharmaceutical composition provides sustained release of bempedoic acid.

15 . A method of treating autosomal dominant polycystic kidney disease (ADPKD) or slowing the progression of ADPKD in a subject receiving tolvaptan therapy or preventing kidney failure in a subject with ADPKD receiving tolvaptan therapy, the method comprising administering to the subject an effective amount of bempedoic acid.

16 . The method of claim 15 , wherein the effective amount of bempedoic acid is about 30 mg to about 240 mg, or about 180 mg.

17 . The method of claim 15 or 16 , wherein the subject receiving the effective amount of bempedoic acid and tolvaptan therapy:

has a lower yearly decrease in estimated glomerular filtration rate than a subject not receiving the effective amount of bempedoic acid and tolvaptan therapy, or receiving only the effective amount of bempedoic acid, or receiving only tolvaptan therapy;

has a lower yearly increase in total kidney volume than a subject not receiving the effective amount of bempedoic acid and tolvaptan therapy, or receiving only the effective amount of bempedoic acid, or receiving only tolvaptan therapy;

has a lower composite incidence of clinical endpoints selected from worsening kidney function, kidney pain, hypertension, and albuminuria than a subject not receiving the effective amount of bempedoic acid and tolvaptan therapy, or receiving only the effective amount of bempedoic acid, or receiving only tolvaptan therapy;

has higher liver AMPK activity than a subject not receiving the effective amount of bempedoic acid, or receiving only tolvaptan therapy;

has a higher degree of liver acetyl-coenzyme A carboxylase (ACC) phosphorylation than a subject not receiving the effective amount of bempedoic acid, or receiving only tolvaptan therapy; and/or

has a higher degree of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) activity than a subject receiving only tolvaptan therapy.

18 . A method of treating autosomal dominant polycystic kidney disease (ADPKD) or slowing the progression of ADPKD in a subject in need thereof or preventing kidney failure in a subject with ADPKD, the method comprising administering to the subject the fixed-dose combination of any one of claims 1-5 and 11-14 , or administering to the subject the pharmaceutical composition of any one of claims 6-10 and 11-14 .

19 . The method of claim 18 , wherein the subject receiving the fixed-dose combination or the pharmaceutical composition:

has a lower yearly decrease in estimated glomerular filtration rate than a subject not receiving the fixed-dose combination, or receiving only about 30 mg to about 240 mg bempedoic acid, or receiving only about 5 mg to about 90 mg tolvaptan;

has a lower yearly increase in total kidney volume than a subject not receiving the fixed-dose combination, or receiving only about 30 mg to about 240 mg bempedoic acid, or receiving only about 5 mg to about 90 mg tolvaptan;

has a lower composite incidence of clinical endpoints selected from worsening kidney function, kidney pain, hypertension, and albuminuria than a subject not receiving the fixed-dose combination, or receiving only about 30 mg to about 240 mg bempedoic acid, or receiving only about 5 mg to about 90 mg tolvaptan;

has higher liver AMPK activity than a subject not receiving the fixed-dose combination, or receiving only about 5 mg to about 90 mg tolvaptan;

has a higher degree of liver acetyl-coenzyme A carboxylase (ACC) phosphorylation than a subject not receiving the fixed-dose combination, or receiving only about 5 mg to about 90 mg tolvaptan;

has a higher degree of liver acetyl-coenzyme A carboxylase (ACC) phosphorylation than a subject not receiving the fixed-dose combination, or receiving only about 5 mg to about 90 mg tolvaptan; and/or

has a higher degree of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) activity than a subject receiving only about 5 mg to about 90 mg tolvaptan.

20 . A method of treating autosomal dominant polycystic kidney disease (ADPKD) or slowing the progression of ADPKD in a subject in need thereof or preventing kidney failure in a subject with ADPKD, the method comprising administering to the subject an effective amount of bempedoic acid.

21 . The method of claim 20 , wherein the effective amount of bempedoic acid is about 30 mg to about 240 mg, or about 180 mg.

22 . The method of claim 20 or 21 , further comprising administering to the subject an effective amount of tolvaptan.

23 . The method of claim 22 , wherein the effective amount of tolvaptan comprises about 5 mg, about 10 mg, about 15 mg, about 30 mg, about 45 mg, about 60 mg, or about 90 mg tolvaptan.

24 . The method of claim 20 or 21 , wherein the subject receiving the effective amount of bempedoic acid, or of claim 22 or 23 wherein the subject receiving the effective amount of bempedoic acid and tolvaptan:

has a lower yearly decrease in estimated glomerular filtration rate than a subject receiving a placebo, or has an equivalent or a lower total kidney weight to body weight ratio than a subject receiving tolvaptan therapy;

has a lower yearly increase in total kidney volume than a subject receiving a placebo, or has an equivalent or a lower blood urea nitrogen level than a subject receiving tolvaptan therapy;

has a lower composite incidence of clinical endpoints selected from worsening kidney function, kidney pain, hypertension, and albuminuria than a subject receiving a placebo, or receiving only bempedoic acid, or receiving only tolvaptan;

has higher liver AMPK activity than a subject receiving a placebo, or receiving only tolvaptan;

has a higher degree of liver acetyl-coenzyme A carboxylase (ACC) phosphorylation than a subject receiving a placebo, or receiving only tolvaptan; and/or

has a higher degree of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) activity than a subject receiving only tolvaptan.

25 . The method of any one of claims 20-24 , wherein the subject receiving the effective amount of bempedoic acid has a lower composite incidence of clinical endpoints selected from worsening kidney function, kidney pain, hypertension, and albuminuria than a subject receiving a placebo, or has an equivalent or a lower composite incidence of clinical endpoints selected from worsening kidney function, kidney pain, hypertension, and albuminuria than a subject receiving tolvaptan therapy.

26 . The method of any one of claims 15-25 , wherein the subject is a human.