Methods of using buffered formulations of exendin (9-39)

Inventors

Xiong, Xiaofeng • Odink, Debra • Craig, Colleen M. • Smith, Christine M. N. • McLaughlin, Tracey L.

Assignees

Leland Stanford Junior University • Amylyx Pharmaceuticals Inc

Abstract

Provided herein are liquid pharmaceutical formulations comprising exendin (9-39) or a pharmaceutically acceptable salt thereof and a tonicity modifier in a physiologically acceptable buffer having a pH in the range of about 5 to about 6. In some embodiments, the buffered liquid formulation comprises exendin (9-39) or a pharmaceutically acceptable salt thereof in an acetate buffer or a citrate buffer. Methods of treating or preventing hyperinsulinemic hypoglycemia in a subject comprising administering to the subject the buffered liquid formulation are also provided.

Core Innovation

The disclosed invention provides buffered liquid pharmaceutical formulations comprising exendin (9-39) or a pharmaceutically acceptable salt thereof together with a tonicity modifier in a physiologically acceptable buffer having a pH in the range of 5.1 to 6. The liquid formulation is formulated for oral, intravenous, buccal, rectal, parenteral, intraperitoneal, intradermal, intramuscular, subcutaneous, and inhalational administration.

A key requirement is that exendin (9-39) or the pharmaceutically acceptable salt thereof does not exhibit detectable aggregation in the pharmaceutical liquid formulation. The invention further includes an improved pharmacokinetic profile relative to a composition comprising the same dose of exendin (9-39) or a pharmaceutically acceptable salt thereof formulated in 0.9% normal saline.

The disclosed formulations are also directed to treating hyperinsulinemic hypoglycemia in a subject by administering the liquid pharmaceutical formulation. The described therapeutic use includes treatment and prevention of hyperinsulinemic hypoglycemia, including post-bariatric hypoglycemia (PBH), such as post-Roux-en-Y gastric bypass.

Claims Coverage

The document contains one independent claim. It covers a method of treating hyperinsulinemic hypoglycemia by administering a tonicity-modified, pH-buffered liquid formulation of exendin (9-39) or a salt, including requirements for non-detectable aggregation and an improved pharmacokinetic profile versus a 0.9% normal saline formulation; it includes multiple administration routes.

Overall, the independent claim requires a buffered liquid formulation of exendin (9-39) with a tonicity modifier, pH 5.1–6, no detectable aggregation, and improved pharmacokinetics compared with the same dose in 0.9% normal saline, while explicitly covering a range of administration routes.

Stated Advantages

Documented Applications