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US-12622899-B2 - Methods of treating idiopathic pulmonary fibrosis with deupirfenidone

US12622899B2US 12622899 B2US12622899 B2US 12622899B2US-12622899-B2

Abstract

Disclosed herein is a method of treating Idiopathic Pulmonary Fibrosis (IPF). The method includes administering to a subject in need thereof the deuterium-enriched pirfenidone LYT-100 at a total daily dose from about 1650 mg to about 2500 mg.

Inventors

  • Michael C. Chen
  • Varun Garg
  • Yanqiong ZHANG
  • Carol Ann Satler
  • David Andrew Golod
  • Eric Elenko
  • Heather A. Paden
  • Christopher C. Korth
  • Paul Andrew Ford
  • Julie S. Krop
  • Camilla S. Graham
  • Liza C. Micioni
  • Simon John Hatch

Assignees

  • PURETECH LYT 100, INC.

Dates

Publication Date
20260512
Application Date
20250814

Claims (6)

  1. 1 . A method of treating Idiopathic Pulmonary Fibrosis (IPF), the method comprising orally administering to a subject in need thereof a total daily dose of 1600 mg to 2500 mg in three equal administrations of a deuterium-enriched pirfenidone having the structure: wherein deupirfenidone provides improved efficacy compared to pirfenidone without a loss of tolerability.
  2. 2 . The method of claim 1 , wherein the subject is orally administered a total daily dose of 2400 mg to 2500 mg of deupirfenidone.
  3. 3 . The method of claim 2 , wherein the subject is orally administered a 2475 mg total daily dose of deupirfenidone.
  4. 4 . The method of claim 1 , wherein the deupirfenidone is orally administered in an oral dose form selected from a capsule or a tablet.
  5. 5 . The method of claim 1 , wherein orally administering a total daily dose of 1650 mg deupirfenidone provides comparable efficacy and improved tolerability relative to treating with a total daily dose 2403 mg pirfenidone.
  6. 6 . The method of claim 1 , wherein orally administering a total daily dose of 2475 mg deupirfenidone provides an approximately 50% greater effect size compared to a total daily dose 2403 mg pirfenidone without a loss of tolerability.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser. No. 19/286,158, filed Jul. 30, 2025, which is a continuation of U.S. application Ser. No. 18/982,798, filed Dec. 16, 2024, which is a continuation-in-part of U.S. application Ser. No. 18/806,289, filed Aug. 15, 2024, which is a continuation of U.S. application Ser. No. 18/437,614, filed Feb. 9, 2024, which is a continuation of U.S. application Ser. No. 18/330,154, filed Jun. 6, 2023, which is a continuation of U.S. application Ser. No. 17/144,018, filed Jan. 7, 2021, which is a continuation of U.S. application Ser. No. 16/572,595, filed Sep. 16, 2019, which claims the benefit of U.S. Provisional Application No. 62/884,984, filed Aug. 9, 2019, and claims the benefit of U.S. Provisional Application No. 62/839,256, filed Apr. 26, 2019, and claims the benefit of U.S. Provisional Application No. 62/750,377, filed Oct. 25, 2018, and claims the benefit of U.S. Provisional Application No. 62/731,570, filed Sep. 14, 2018; and said Ser. No. 18/982,798 is also a continuation-in-part of U.S. application Ser. No. 18/758,783, filed Jun. 28, 2024, which is a continuation of International Application No. PCT/US2023/060185, filed Jan. 5, 2023, which claims the benefit of U.S. Provisional Application No. 63/432,208, filed Dec. 13, 2022, and claims the benefit of U.S. Provisional Application No. 63/431,530, filed Dec. 9, 2022, and claims the benefit of U.S. Provisional Application No. 63/403,481, filed Sep. 2, 2022, and claims the benefit of U.S. Provisional Application No. 63/374,362, filed Sep. 1, 2022, and claims the benefit of U.S. Provisional Application No. 63/356,653, filed Jun. 29, 2022, and claims the benefit of U.S. Provisional Application No. 63/352,107, filed Jun. 14, 2022, and claims the benefit of U.S. Provisional Application No. 63/341,828, filed May 13, 2022, and claims the benefit of U.S. Provisional Application No. 63/341,269, filed May 12, 2022, and claims the benefit of U.S. Provisional Application No. 63/341,279, filed May 12, 2022, and claims the benefit of U.S. Provisional Application No. 63/341,281, filed May 12, 2022, and claims the benefit of U.S. Provisional Application No. 63/326,132, filed Mar. 31, 2022, and claims the benefit of U.S. Provisional Application No. 63/326,129, filed Mar. 31, 2022, and claims the benefit of U.S. Provisional Application No. 63/296,818, filed Jan. 5, 2022, and claims the benefit of U.S. Provisional Application No. 63/296,843, filed Jan. 5, 2022, and claims the benefit of U.S. Provisional Application No. 63/296,826, filed Jan. 5, 2022; and said Ser. No. 18/982,798 is also a continuation-in-part of U.S. application Ser. No. 18/150,055, filed Jan. 4, 2023, which is a continuation of International Application No. PCT/US2021/040551, filed Jul. 6, 2021, which claims the benefit of U.S. Provisional Application No. 63/175,063, filed Apr. 15, 2021, and claims the benefit of U.S. Provisional Application No. 63/135,374, filed Jan. 8, 2021, and claims the benefit of U.S. Provisional Application No. 63/123,989, filed Dec. 10, 2020, and claims the benefit of 63/121,168, filed Dec. 3, 2020, and claims the benefit of U.S. Provisional Application No. 63/116,520, filed Nov. 20, 2020, and claims the benefit of U.S. Provisional Application No. 63/087,116, filed Oct. 2, 2020, and claims the benefit of U.S. Provisional Application No. 63/048,564, filed Jul. 6, 2020. BACKGROUND There exists a need for a therapy that can slow disease progression in patients with idiopathic pulmonary fibrosis (IPF) while having a superior tolerability profile compared to pirfenidone and other antifibrotics approved for treatment of IPF. High doses of pirfenidone are required to achieve efficacy in the treatment of IPF. However, tolerability issues, including dose-limiting side effects and toxicity associated with gastrointestinal intolerability (e.g., nausea, diarrhea, vomiting, dyspepsia, and other GI events), headache, dizziness, and photosensitivity, as well as other adverse side-effects, limits current treatment for IPF. Such dose-limiting side effects and/or toxicity typically require, and are therefore managed by, one or more of the following treatment options: administration of lower, less efficacious doses, periodic reduction(s) of efficacious dose, periodic or permanent cessation of drug (treatment interruption or discontinuation), and/or inability to maintain patients on a sustained treatment program or long-term maintenance dose (e.g., without treatment interruption). These tolerability issues significantly limit the usage of pirfenidone, resulting in dose reduction, switch of drug, and/or interruption or discontinuation of antifibrotic therapy. It is estimated that about 75% of IPF patients are not on standard of care therapy as a consequence of poor drug tolerability, and that over 40% of patients eventually discontinue antifibrotic therapy, in large part due to tolerability issues (FIG. 1A). In part