PHARMACEUTICAL COMPOSITION CONTAINING DIMETHYL FUMARATE FOR ADMINISTRATION AT A LOW DAILY DOSE

1 . A pharmaceutical composition for oral use in treating multiple sclerosis, wherein said composition is in the form of an erosion matrix tablet comprising a tablet core and one or more coating(s), wherein the tablet core comprises

i) 10 to 80% by weight dimethyl fumarate as the active substance, and

ii) 1 to 50% by weight of one or more rate-controlling agents,

wherein at least one of the one or more coating(s) is an enteric coating applied at a level of 1.5 to 3.5% by weight of the core, and

wherein the dose of dimethyl fumarate to be administered orally to a subject in need of treatment for multiple sclerosis is 410 mg±5% per day or 400 mg±5% per day.

2 . The pharmaceutical composition according to claim 1 , wherein the dose to be administered is 410 mg or 400 mg per day.

3 . The pharmaceutical composition according to claim 1 or 2 , wherein the tablet core comprises

i) 30 to 60% by weight of dimethyl fumarate; and

ii) 3 to 40% by weight of one or more rate-controlling agents.

4 . The pharmaceutical composition according to claim 3 , wherein the rate-controlling agent is a water-soluble polymer.

5 . The pharmaceutical composition according to any one of claims 1 - 4 , wherein the rate-controlling agent is a cellulose polymer or a cellulose derivative or a mixture thereof.

6 . The pharmaceutical composition according to any one of the previous claims, wherein the rate-controlling agent is selected from the group comprising hydroxypropyl cellulose, hydroxypropyl methyl cellulose (HPMC), methyl cellulose, carboxymethyl cellulose and mixtures thereof.

7 . The pharmaceutical composition according to claim 6 , wherein the rate-controlling agent is hydroxypropyl cellulose.

8 . The pharmaceutical composition according to any one of the preceding claims, wherein the tablet core further comprises a binder.

9 . The pharmaceutical composition according to claim 8 , wherein the binder is lactose.

10 . The pharmaceutical composition according to any one of the preceding claims, wherein the tablet core comprises:

i) 35-55% by weight of dimethyl fumarate;

ii) 3-12% by weight of hydroxypropyl cellulose; and

iii) 40-60% by weight of lactose.

11 . The pharmaceutical composition according to any one of the preceding claims, wherein the tablet core comprises:

i) 35-50% by weight of dimethyl fumarate;

ii) 3-12% by weight of hydroxypropyl cellulose; and

iii) 45-60% by weight of lactose.

12 . The pharmaceutical composition according to any one of the preceding claims, wherein the tablet core comprises:

i) 35-50% by weight of dimethyl fumarate;

ii) 3-10% by weight of hydroxypropyl cellulose; and

iii) 45-60% by weight of lactose.

13 . The pharmaceutical composition according to claim 11 or 12 , wherein the amount of hydroxypropyl cellulose is 3-6% by weight.

14 . The pharmaceutical composition according to any one of the preceding claims, wherein the tablet core further comprises 0.15-0.7% by weight of magnesium stearate and, optionally, 0.05 to 0.25% by weight of silicon dioxide.

15 . A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof 410 mg±5% per day or 400 mg±5% per day dimethylfumarate in a pharmaceutical composition of any one of claims 1 - 14 .

16 . The method of claim 15 , wherein multiple sclerosis includes relapsing remitting or progressive multiple sclerosis.

17 . The method of any one of claims 15 - 16 , wherein the pharmaceutical composition is administered once, twice or three times daily.

18 . The method of claim 17 , wherein 410 mg±5% per day dimethylfumarate is administered in two equal doses at different times of the day.

19 . The method of claim 18 , wherein about 205 mg dimethylfumarate is administered in the morning and the remainder is administered later in the day.

20 . The method of claim 17 , wherein 400 mg±5% per day dimethylfumarate is administered in two equal doses at different times of the day.

21 . The method of claim 20 , wherein about 200 mg dimethylfumarate is administered in the morning and the remainder is administered later in the day.

22 . A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof 410 mg±5% per day or 400 mg±5% per day dimethylfumarate.

23 . The method of claim 22 , wherein multiple sclerosis includes relapsing remitting or progressive multiple sclerosis.

24 . The method of any one of claims 20 - 23 , wherein the dimethylfumarate is formulated in a unit dosage form and the unit dosage form is administered once, twice or three times daily.

25 . The method of claim 24 , wherein 410 mg±5% per day dimethylfumarate is administered in two equal doses at different times of the day.

26 . The method of claim 25 , wherein about 205 mg dimethylfumarate is administered in the morning and the remainder is administered later in the day.

27 . The method of claim 24 , wherein 400 mg±5% per day dimethylfumarate is administered in two equal doses at different times of the day.

28 . The method of claim 27 , wherein about 200 mg dimethylfumarate is administered in the morning and the remainder is administered later in the day.