Laquinimod Combination Therapy For Treatment Of Multiple Sclerosis

A package comprising:

• a) a first pharmaceutical composition comprising an amount of laquinimod or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier;
• b) a second pharmaceutical composition comprising an amount of a compound of formula (I):
• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3,
• or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier;
• and
• c) instruction for use for the first and the second pharmaceutical composition together to treat a subject afflicted with a form of MS or presenting a CIS.

A pharmaceutical composition comprising an amount of laquinimod or a pharmaceutically acceptable salt thereof and an amount of a compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3,
• or a pharmaceutically acceptable salt thereof,
• and at least one pharmaceutically acceptable carrier.

A pharmaceutical composition in unit dosage form, useful in treating a subject afflicted with MS or presenting a CIS, which comprises:

• a) an amount of laquinimod or a pharmaceutically acceptable salt thereof;
• b) an amount of a compound of formula (I):
• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof,
• wherein the respective amounts of said laquinimod and said compound of formula (I) in said composition are effective, upon concomitant administration to said subject of one or more of said unit dosage forms of said composition, to treat the subject.

A pharmaceutical composition comprising an amount of laquinimod or a pharmaceutically acceptable salt thereof for use in treating a subject afflicted with MS or presenting a CIS as an add-on therapy or in combination with, or simultaneously, contemporaneously or concomitantly with a compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition comprising an amount of a compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof,
• for use treating a subject afflicted with MS or presenting a CIS as an add-on therapy or in combination with, or simultaneously, contemporaneously or concomitantly with laquinimod or a pharmaceutically acceptable salt thereof.

Use of:

• a) an amount of laquinimod or pharmaceutically acceptable salt thereof;
• and
• b) an amount of a compound of formula (I):
• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or pharmaceutically acceptable salt thereof,
• in the preparation of a combination for treating a subject afflicted with MS or presenting a CIS wherein the amount of laquinimod and the amount of the compound of formula (I) are administered simultaneously or contemporaneously.

Laquinimod for use as an add-on therapy or in combination with a compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof, in treating a subject afflicted with MS or presenting a CIS.

A compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof,
• for use as an add-on therapy or in combination with laquinimod or a pharmaceutically acceptable salt thereof in treating a subject afflicted with MS or presenting a CIS.

Laquinimod or a pharmaceutically acceptable salt thereof and a compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof,
• for the treatment of a subject afflicted with MS or presenting a CIS, wherein the laquinimod and the compound of formula (I) are administered simultaneously, separately or sequentially.

A product containing an amount of laquinimod or a pharmaceutically acceptable salt thereof and an amount of a compound of formula (I):

• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, and, or a pharmaceutically acceptable salt thereof,
• for simultaneous, separate or sequential use in treating a subject afflicted with MS or presenting a CIS.

A therapeutic package for dispensing to, or for use in dispensing to, a subject afflicted with MS or presenting a CIS, which comprises:

• a) one or more unit doses, each such unit dose comprising:
• i) an amount of laquinimod or a pharmaceutically acceptable salt thereof and
• ii) an amount a compound of formula (I):
• wherein
• R1 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• R2 is H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl or C3-C8 cycloalkyl;
• and
• when one of R1 or R2 is CH3, then the other of R1 or R2 is other than CH3, or a pharmaceutically acceptable salt thereof
• wherein the respective amounts of said laquinimod and said compound of formula (I) in said unit dose are effective, upon concomitant administration to said subject, to treat the subject, and
• b) a finished pharmaceutical container therefor, said container containing said unit dose or unit doses, said container further containing or comprising labeling directing the use of said package in the treatment of said subject.