US 12,138,246 B2
Treatments with nirogacestat
Allison Lim, Stamford, CT (US); Shinta Cheng, Stamford, CT (US); Todd Webster Shearer, Stamford, CT (US); Rex Williams, Stamford, CT (US); and Kristin Patterson, Stamford, CT (US)
Assigned to SPRINGWORKS THERAPEUTICS, INC., Stamford, CT (US)
Filed by SpringWorks Therapeutics, Inc., Stamford, CT (US)
Filed on Apr. 2, 2024, as Appl. No. 18/624,670.
Application 18/624,670 is a continuation in part of application No. 18/543,022, filed on Dec. 18, 2023, granted, now 12,036,207.
Application 18/543,022 is a continuation in part of application No. 18/491,525, filed on Oct. 20, 2023, granted, now 11,951,096.
Application 18/491,525 is a continuation in part of application No. 18/320,547, filed on May 19, 2023, granted, now 11,872,211, issued on Jan. 16, 2024.
Claims priority of provisional application 63/365,193, filed on May 23, 2022.
Claims priority of provisional application 63/365,125, filed on May 20, 2022.
Prior Publication US 2024/0245648 A1, Jul. 25, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/417 (2006.01); A61K 9/00 (2006.01); A61P 35/00 (2006.01)
CPC A61K 31/417 (2013.01) [A61K 9/0053 (2013.01); A61P 35/00 (2018.01)] 28 Claims
 
1. A method for treating therapeutic treatment of desmoid tumor in a patient in need thereof comprising orally administering to the patient 150 mg (free base equivalent dose) of nirogacestat or a pharmaceutically acceptable salt thereof twice daily without concomitant administration of a moderate or strong CYP3A inhibitor or a moderate or strong CYP3A inducer, wherein the method further comprises one or more of:
(a) upon the patient having Grade 3 or 4 diarrhea persisting for at least 3 days despite medical therapy, withholding the nirogacestat or pharmaceutically acceptable salt thereof until the diarrhea is resolved to no higher than a Grade 1 diarrhea 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;
(b) upon the patient having Grade 3 or 4 hypophosphatemia persisting for at least 3 days despite replacement therapy, withholding the nirogacestat or pharmaceutically acceptable salt thereof until the hypophosphatemia is resolved to no higher than a Grade 1 hypophosphatemia 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;
(c) upon the patient having Grade 3 or 4 hypokalemia despite replacement therapy, withholding the nirogacestat or pharmaceutically acceptable salt thereof until the hypokalemia is resolved to no higher than a Grade 1 hypokalemia 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;
(d) 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 less 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; and
(e) 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.