Granted Patent B2

US 12,409,172 · App. 18/790,828 · Granted Sep 9, 2025

Inventors: Morten Otto Alexander Sommer (Hellerup, DK); Jakob Felding (Hellerup, DK); Kim Domela Kjøller (Hellerup, DK); Mads Jellingsø (Hellerup, DK); Morten Lind Jensen (Hellerup, DK); Eckhard Niemeier (Hellerup, DK)

Assignee: UNION therapeutics A/S

A61K31/4436A61K9/0053A61K9/20A61P17/06

Abstract

Claims (141)

1. A method of treating a disease selected from psoriasis and atopic dermatitis in a subject, the method comprising orally administering orismilast to the subject, wherein:

(Ai) (i) an initial orismilast dose of 10 mg is administered to the subject once per day for two weeks if the subject has body mass of less than 60 kg, or

(ii) an initial orismilast dose of 20 mg is administered to the subject once per day for two weeks if the subject has body mass of greater than or equal to 60 kg;

followed by

(Aii) (i) an interim orismilast dose of 10 mg administered to the subject twice per day for an interim time period if the subject has body mass of less than 60 kg; or

(ii) an interim orismilast dose of 20 mg administered to the subject twice per day for an interim time period if the subject has body mass of greater than or equal to 60 kg;

followed by;

(Aiii) (i) a maintenance orismilast dose of 10 mg administered to the subject twice per day if the subject has a body mass of less than 60 kg, or

(ii) a maintenance orismilast dose of 20 mg administered to the subject twice per day if the subject has body mass of greater than or equal to 60 kg to less than 100 kg, or

(iii) a maintenance orismilast dose of 30 mg administered to the subject twice per day if the subject has a body mass of greater than or equal to 100 kg;

wherein the interim time period is one to eight weeks.

2. The method according to claim 1 , wherein the interim time period is two weeks.

3. The method according to claim 1 , wherein the interim time period is four weeks.

4. The method according to claim 1 , wherein the interim time period is six weeks.

5. The method according to claim 1 , wherein the interim time period is eight weeks.

6. The method according to claim 1 , wherein the disease is psoriasis.

7. The method according to claim 1 , wherein the disease is moderate to severe plaque-type psoriasis.

8. The method according to claim 7 , wherein:

(i) the subject has a 75% reduction in PASI (PASI75) from baseline after 16 weeks of treatment; or

(ii) the subject has a 90% reduction in PASI (PASI90) from baseline after 16 weeks of treatment; or

(iii) the subject has a 100% reduction in PASI (PASI100) from baseline after 16 weeks of treatment; or

(iii) the subject achieves a Investigator Global Assessment (IGA) of clear (0) or almost clear (1) after 16 weeks of treatment.

9. The method according to claim 1 , wherein the disease is atopic dermatitis.

10. The method according to claim 1 , wherein the disease is moderate to severe atopic dermatitis.

11. The method of claim 10 , wherein:

(i) the subject has a 75% reduction in EASI (EASI75) from baseline after 16 weeks of treatment; or

(ii) the subject has a 90% reduction in EASI (EASI90) from baseline after 16 weeks of treatment; or

(iii) the subject has a 100% reduction in EASI (EASI100) from baseline after 16 weeks of treatment; or

(iv) the subject achieves an Investigator Global Assessment for AD (IGA-AD) score of clear (0) or almost clear (1) and at least a 2-point improvement in IGA-AD from baseline after 16 weeks of treatment; or

(v) the subject achieves an Investigator Global Assessment for AD (IGA-AD) score of clear (0) after 16 weeks of treatment.

12. The method according to claim 1 , wherein the orismilast is orally administered to the subject in the form of a modified release formulation comprising the orismilast.

13. The method according to claim 12 , wherein the modified release formulation releases a mean amount of about 10% to about 70% of the orismilast after 45 minutes and more than about 70% after 180 minutes, when measured in-vitro using Ph. Eur. 2.9.3 Apparatus II, with a dissolution medium of 900 ml 0.5% sodium dodecyl sulfate in 0.1N HCl, a paddle speed of 75 rpm, and the dissolution medium at 37±0.5° C.

14. The method according to claim 12 , wherein the modified release formulation comprises orismilast and a polymeric matrix.

15. The method according to claim 14 , wherein the polymer matrix comprises a hydrophilic or hydrophobic matrix.

16. The method according to claim 14 , wherein the polymer matrix is selected from one or more polymers selected from hydroxypropyl methylcellulose, methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose a polyethylene oxide, a polyethylene glycol, a polyethyleneoxide-polypropyleneoxide block-co-polymer, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, polyvinylpyrrolidone (PVP), a copolymers of PVP and vinyl acetate, a poly (ethylene-vinyl acetate), polyvinyl alcohol, a sugar alcohol and a biodegradable polymer.

17. The method of claim 14 , wherein the polymeric matrix comprises hydroxypropyl methylcellulose.

18. The method of claim 12 , wherein the modified release formulation comprises of from about 15% w/w to about 20% w/w hydroxypropyl methylcellulose, wherein a 2% solution of the hydroxypropyl methylcellulose in water at 20° C. has a viscosity of from 80 to 120 mPa·s.

19. The method of claim 12 , wherein the modified release formulation comprises a core comprising:

(i) orismilast;

(ii) a hydrophilic matrix former, wherein the hydrophilic matrix former is present in a concentration of from about 15% w/w to about 20% w/w hydroxypropyl methylcellulose based on the weight of the core;

(iii) from about 30% w/w to about 78% w/w lactose monohydrate based on the weight of the core; and

(iv) optionally one or more pharmaceutically acceptable excipients selected from the group consisting of glidants and lubricants;

wherein the composition further comprises a pharmaceutically acceptable coating system on the core.

20. The method of claim 19 , wherein a 2% solution of the hydroxypropyl methylcellulose in water at 20° C. has a viscosity of from 80 to 120 mPa·s; and the pharmaceutically acceptable coating system is a PVA-based coating system.

21. The method of claim 12 , wherein the modified release formulation comprises Core 1, Core 2 or Core 3 selected from Table A or Core 4, Core 5 or Core 6 selected from Table B:

TABLE A

% w/w of the core

Component

Core 1

Core 2

Core 3

orismilast

 2.5-4.5%

 5.5-7.7%

   9-11%

Lactose monohydrate

 70-85%

 69-80%

 66-76%

Hydroxypropyl

 12-23%

 12-23%

 12-23%

methylcellulose

Anhydrous colloidal

0.01-1.5%

0.01-1.5%

0.01-1.5%

silica

Magnesium stearate

0.01-2.0%

0.01-2.0%

0.01-2.0%

wherein the core in Table A is coated with a water-soluble film coating in an amount to provide about 3% to 5% weight gain of the core;

TABLE B

Amount

Component

Core 4

Core 5

Core 6

orismilast

10

mg

20

mg

30

mg

Lactose monohydrate

233

mg

223

mg

213

mg

Hydroxypropyl

52.5

mg

52.5

mg

52.5

mg

methylcellulose

Anhydrous colloidal

1.5

mg

1.5

mg

1.5

mg

silica

Magnesium stearate

3.0

mg

3.0

mg

3.0

mg

Core weight

300

mg

300

mg

300

mg

Water-soluble film

12

mg

12

mg

12

mg

coating

Coated core weight

312

mg

312

mg

312

mg.

22. The method of claim 21 , wherein a 2% solution of the hydroxypropyl methylcellulose in water at 20° C. has a viscosity of from 80 to 120 mPa·s; and the water-soluble film coating is a PVA-based pharmaceutically acceptable coating system is a polyvinyl alcohol-based coating.

23. The method of claim 22 , wherein the hydroxypropyl methylcellulose in Core 1, Core 2 and Core 3 is present in an amount of about 17.5% w/w of the core.

Assignments (1)

Priority Claims (1)

Continuity (2)

References Cited (231)