Treatments with nirogacestat

Patent metadata

Field	Value
Publication number	US-11925619-B2
Application number	US-202318361884-A
Country	US
Kind code	B2
Filing date	Jul 30, 2023
Priority date	May 20, 2022
Publication date	Mar 12, 2024
Grant date	Mar 12, 2024

Abstract

The present disclosure relates to improved methods of treatment with nirogacestat.

First claim

What is claimed:

1. A method for therapeutic treatment of desmoid tumor in a patient in need thereof comprising administering to the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof, wherein the oral dosage provides upon initial oral administration to the patient a C max of less than 1000 ng/mL, wherein
the method comprises orally administering to the patient 150 mg (free base equivalent dose) of nirogacestat or a pharmaceutically acceptable salt thereof twice daily, and
the method further comprises upon the patient having an alanine transaminase (ALT) or aspartate aminotransferase (AST) of 3 to 5 times upper limit of normal (ULN), withholding the nirogacestat or pharmaceutically acceptable salt thereof until the ALT, AST, or both are resolved to no higher than 3 times ULN or baseline and then restarting oral administration of the nirogacestat or pharmaceutically acceptable salt thereof at a dose of 100 mg (free base equivalent dose) twice daily.

2. The method of claim 1 , wherein the oral dosage is administered once daily.

3. The method of claim 1 , wherein the oral dosage is administered twice daily.

4. The method of claim 1 , wherein the desmoid tumor is progressive desmoid tumor.

5. The method of claim 1 , wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides a reduction in the risk of disease progression.

6. The method of claim 1 , wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvement of progression-free survival.

7. The method of claim 1 , wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvements in objective response rate and at least one quality of life assessment.

8. A method for therapeutic treatment of desmoid tumor in a patient in need thereof comprising administering to the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof, wherein the oral dosage provides upon initial oral administration to a human subject an AUC inf of less than 4000 ng·h/mL, wherein
the method comprises orally administering to the patient 150 mg (free base equivalent dose) of nirogacestat or a pharmaceutically acceptable salt thereof twice daily, and
the method further comprises upon the patient having an alanine transaminase (ALT) or aspartate aminotransferase (AST) of 3 to 5 times upper limit of normal (ULN), withholding the nirogacestat or pharmaceutically acceptable salt thereof until the ALT, AST, or both are resolved to no higher than 3 times ULN or baseline and then restarting oral administration of the nirogacestat or pharmaceutically acceptable salt thereof at a dose of 100 mg (free base equivalent dose) twice daily.

9. The method of claim 8 , wherein the oral dosage is administered once daily.

10. The method of claim 8 , wherein the oral dosage is administered twice daily.

11. The method of claim 8 , wherein the desmoid tumor is progressive desmoid tumor.

12. The method of claim 8 , wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides a reduction in the risk of disease progression.

13. The method of claim 8 , wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvement of progression-free survival.

14. The method of claim 8 , wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvements in objective response rate and at least one quality of life assessment.

15. The method of claim 1 , wherein the method further comprises upon the patient having an ALT or AST of greater than 5 times ULN, permanently discontinuing treatment with the nirogacestat or pharmaceutically acceptable salt thereof.

16. The method of claim 8 , wherein the method further comprises upon the patient having an ALT or AST of greater than 5 times ULN, permanently discontinuing treatment with the nirogacestat or pharmaceutically acceptable salt thereof.

Assignees

• Springworks Therapeutics Inc

Inventors

• Lim Allison
• Cheng Shinta
• Shearer Todd Webster
• Williams Rex
• Patterson Kristin

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K31/417 Primary

  Imidazole-alkylamines, e.g. histamine, phentolamine · CPC title

• A61K31/4164 Primary

  1,3-Diazoles · CPC title