Methods for treating heterotopic ossification

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs 60 kg or more, the method comprising:

• (i) during the quiescent period administering daily to the subject 400 mg or 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 20 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 10 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs 60 kg or more, the method comprising:

• (i) during the quiescent period administering daily to the subject 400 mg or 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 15 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 7.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs 40 to 60 kg, the method comprising:

• (i) during the quiescent period administering daily to the subject 400 mg or 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 15 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 7.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs 40 to 60 kg, the method comprising:

• (i) during the quiescent period administering daily to the subject 400 mg or 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 12.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs 20 to 40 kg, the method comprising:

• (i) during the quiescent period administering daily to the subject 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 12.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 6 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs 20 to 40 kg, the method comprising:

• (i) during the quiescent period administering daily to the subject 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 10 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 4 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs less than 20 kg, the method comprising:

• (i) during the quiescent period administering daily to the subject 400 mg or 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 10 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject with FOP characterized by a quiescent period and a non-quiescent period, wherein the subject weighs less than 20 kg, the method comprising:

• (i) during the quiescent period administering daily to the subject 400 mg or 340 mg/m2 of imatinib, or a pharmaceutically acceptable salt thereof, and
• (ii) during the non-quiescent period administering daily to the subject 7.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 28 days, followed by administering daily to the subject 3 mg of palovarotene, or a pharmaceutically acceptable salt thereof, for 56 days,
• wherein during the quiescent period no palovarotene, or a pharmaceutically acceptable salt thereof, is administered to the subject.

A method of treating a subject under 18 years of age with fibrodysplasia ossificans progressiva (FOP) characterized by a quiescent period and a non-quiescent period, the method comprising:

• (i) providing a subject weighing greater than 60 kg with FOP,
• (ii) determining the skeletal maturity of the subject,
• (iii) on the basis of step (ii), if the subject is skeletally immature administering to the subject a daily loading dose of 15.0±1.0 mg followed by a daily maintenance dose of 7.5±1.0 mg of palovarotene, or a pharmaceutically acceptable salt thereof, during the non-quiescent period, or if the subject is skeletally mature administering to the subject a daily loading dose of 20.0±1.0 mg followed by a daily maintenance dose of 10.0±1.0 mg of palovarotene, or a pharmaceutically acceptable salt thereof, during the non-quiescent period.

A method of treating a subject under 18 years of age with fibrodysplasia ossificans progressiva (FOP) characterized by a quiescent period and a non-quiescent period, the method comprising:

• (i) providing a subject weighing 40 to 60 kg with FOP,
• (ii) determining the skeletal maturity of the subject,
• (iii) on the basis of step (ii), if the subject is skeletally immature administering to the subject a daily loading dose of 15.0±2.5 mg followed by a daily maintenance dose of 7.5±2.5 mg of palovarotene, or a pharmaceutically acceptable salt thereof, during the non-quiescent period, or if the subject is skeletally mature administering to the subject a daily loading dose of 20.0±1.0 mg followed by a daily maintenance dose of 10.0±1.0 mg of palovarotene, or a pharmaceutically acceptable salt thereof, during the non-quiescent period.

A method of treating a subject under 18 years of age with fibrodysplasia ossificans progressiva (FOP) characterized by a quiescent period and a non-quiescent period, the method comprising:

• (i) providing a subject weighing 30 to 40 kg with FOP,
• (ii) determining the skeletal maturity of the subject,
• (iii) on the basis of step (ii), if the subject is skeletally immature administering to the subject a daily loading dose of 12.5±2.5 mg followed by a daily maintenance dose of 6.0±2.0 mg of palovarotene, or a pharmaceutically acceptable salt thereof, during the non-quiescent period, or if the subject is skeletally mature administering to the subject a daily loading dose of 20.0±1.0 mg followed by a daily maintenance dose of 10.0±1.0 mg of palovarotene, or a pharmaceutically acceptable salt thereof, during the non-quiescent period.