METHODS OF SLOWING BRAIN VOLUME LOSS
The disclosure relates to methods of slowing brain volume loss. In certain aspects, methods of slowing brain volume loss in a patient with multiple sclerosis are disclosed.
1 . A method of slowing brain volume loss in a patient in need thereof, comprising administering ponesimod to the patient using a regimen that is effective to slow brain volume loss.
2 . A method of slowing brain volume loss in a patient in need thereof, comprising
assessing cognitive deficiencies or physical deficiencies in the patient; and
administering ponesimod to the patient using a regimen that is effective to slow brain volume loss.
3 . A method of slowing brain volume loss in a patient in need thereof, comprising administering ponesimod to the patient using a regimen that is effective to slow brain volume loss relative to a patient population having substantially similar baseline disease characteristics and receiving a standard of care treatment that does not comprise ponesimod.
4 . The method of claim 1 , wherein the patient has multiple sclerosis (MS).
5 . The method of claim 4 , wherein the multiple sclerosis is relapsing multiple sclerosis.
6 . The method of claim 5 , wherein the relapsing multiple sclerosis comprises relapsing-remitting disease, clinically isolated syndrome, or active secondary progressive disease.
7 . The method of claim 1 , wherein about 20 mg of ponesimod is administered orally once daily.
8 . The method of claim 1 , wherein the regimen comprises an up-titration step at initiation of the method or upon re-initiation of the method after a discontinuation, comprising administering orally once daily 2 mg of ponesimod on days 1 and 2; 3 mg of ponesimod on days 3 and 4; 4 mg of ponesimod on days 5 and 6; 5 mg of ponesimod on day 7; 6 mg of ponesimod on day 8; 7 mg of ponesimod on day 9; 8 mg of ponesimod on day 10; and 9 mg of ponesimod on day 11; 10 mg of ponesimod on days 12, 13, and 14, followed by the administering of the 20 mg of ponesimod once daily thereafter.
9 . The method of claim 1 , wherein the brain volume loss comprises loss of white matter or loss of grey matter in the brain.
10 . The method of claim 1 , wherein comprising administering an additional therapeutic agent in combination with the ponesimod.
11 . The method of claim 10 , wherein the additional therapeutic agent is teriflunomide, leflunomide, methyl fumarate, dimethyl fumarate, (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate, or 2-(2,5-dioxopyrrolidin-1-yl)ethyl methyl (2E)but-2-ene-1,4-dioate.
12 . The method of claim 2 , wherein the cognitive deficiencies are associated with information processing; memory; attention/concentration; executive functions;
visuospatial functions; or verbal fluency.
13 . The method of claim 2 , wherein the physical deficiencies are associated with vision, hearing, speaking, swallowing, breathing, muscle weakness, hand-eye coordination, balance, or gait.
14 . The method of claim 3 , wherein the relative slowing of brain volume loss is at least about 20%.
15 . The method of claim 3 , wherein the relative slowing of brain volume loss results after at least about a two year time period from initiation of treatment.
16 . The method of claim 3 , wherein the standard of care treatment comprises teriflunomide.
17 . The method of claim 16 , wherein the standard of care treatment comprises administration of about 14 mg of teriflunomide orally once daily.
18 .- 48 . (canceled)
49 . The method of claim 2 , wherein the patient has multiple sclerosis (MS).
50 . The method of claim 49 , wherein the multiple sclerosis is relapsing multiple sclerosis.
51 . The method of claim 50 , wherein the relapsing multiple sclerosis comprises relapsing-remitting disease, clinically isolated syndrome, or active secondary progressive disease.
52 . The method of claim 2 , wherein about 20 mg of ponesimod is administered orally once daily.
53 . The method of claim 2 , wherein the regimen comprises an up-titration step at initiation of the method or upon re-initiation of the method after a discontinuation, comprising administering orally once daily 2 mg of ponesimod on days 1 and 2; 3 mg of ponesimod on days 3 and 4; 4 mg of ponesimod on days 5 and 6; 5 mg of ponesimod on day 7; 6 mg of ponesimod on day 8; 7 mg of ponesimod on day 9; 8 mg of ponesimod on day 10; and 9 mg of ponesimod on day 11; 10 mg of ponesimod on days 12, 13, and 14, followed by the administering of the 20 mg of ponesimod once daily thereafter.
54 . The method of claim 2 , wherein the brain volume loss comprises loss of white matter or loss of grey matter in the brain.
55 . The method of claim 2 , comprising administering an additional therapeutic agent in combination with the ponesimod.
56 . The method of claim 55 , wherein the additional therapeutic agent is teriflunomide, leflunomide, methyl fumarate, dimethyl fumarate, (N,N-diethylcarbamoyl) methyl methyl (2E)but-2-ene-1,4-dioate, or 2-(2,5-dioxopyrrolidin-1-yl)ethyl methyl (2E)but-2-ene-1,4-dioate.
57 . The method of claim 3 , wherein the patient has multiple sclerosis (MS).
58 . The method of claim 57 , wherein the multiple sclerosis is relapsing multiple sclerosis.
59 . The method of claim 58 , wherein the relapsing multiple sclerosis comprises relapsing-remitting disease, clinically isolated syndrome, or active secondary progressive disease.
60 . The method of claim 3 , wherein about 20 mg of ponesimod is administered orally once daily.
61 . The method of claim 3 , wherein the regimen comprises an up-titration step at initiation of the method or upon re-initiation of the method after a discontinuation, comprising administering orally once daily 2 mg of ponesimod on days 1 and 2; 3 mg of ponesimod on days 3 and 4; 4 mg of ponesimod on days 5 and 6; 5 mg of ponesimod on day 7; 6 mg of ponesimod on day 8; 7 mg of ponesimod on day 9; 8 mg of ponesimod on day 10; and 9 mg of ponesimod on day 11; 10 mg of ponesimod on days 12, 13, and 14, followed by the administering of the 20 mg of ponesimod once daily thereafter.
62 . The method of claim 3 , wherein the brain volume loss comprises loss of white matter or loss of grey matter in the brain.
63 . The method of claim 3 , comprising administering an additional therapeutic agent in combination with the ponesimod.
64 . The method of claim 63 , wherein the additional therapeutic agent is teriflunomide, leflunomide, methyl fumarate, dimethyl fumarate, (N,N-diethylcarbamoyl) methyl methyl (2E)but-2-ene-1,4-dioate, or 2-(2,5-dioxopyrrolidin-1-yl)ethyl methyl (2E)but-2-ene-1,4-dioate.