A randomized phase 1 evaluation of deupirfenidone, a novel deuterium-containing drug candidate for interstitial lung disease and other inflammatory and fibrotic diseases
Abstract
LYT-100 (deupirfenidone) is a selectively deuterated form of pirfenidone under development for the treatment of inflammatory and fibrotic diseases, including interstitial lung disease. Adverse events associated with antifibrotics can be a barrier to adoption and persistence in patients with interstitial lung diseases, most of whom are not on standard-of-care therapy. LYT-100 is designed to have a differentiated pharmacokinetic (PK) profile from pirfenidone and could offer a differentiated safety profile compared to current standard-of-care drugs while retaining the biochemical potency and specificity of pirfenidone. We conducted a phase 1b study to ascertain the safety, tolerability, steady-state PK profile, and food effect of LYT-100. This was a 2-part study. Part 1 assessed multiple ascending doses of LYT-100 from 100, 250, 500, 750, and 1000 mg twice daily given over 5 days without titration. Part 2 assessed the effects of fed vs fasting conditions on the PK profile of a single 500-mg dose of LYT-100. All doses up to 1000 mg were well tolerated, with adverse events being mild and transient. Exposure was slightly lower in the fed condition. LYT-100 was well tolerated and has a dose-proportional PK profile. The ratio of parent to major metabolite concentration was higher than reported with pirfenidone, which is consistent with an effect of deuteration on metabolism. No maximum tolerated dose was identified up to 1000 mg twice-daily dosing. These results support further clinical development of LYT-100, particularly considering the adverse event profile of current standard-of-care drugs.
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Deupirfenidone is a selectively deuterated analog of pirfenidone, with three deuterium atoms replacing hydrogen in the methyl group.
“Deupirfenidone is a selectively deuterated analog of pirfenidone, with three deuterium (heavy hydrogen) atoms replacing hydrogen in the methyl group.11”
From Deupirfenidone Compared with Pirfenidone and Placebo in Idiopathic Pulmonary Fibrosis (ELEVATE-IPF): a Phase 2b Randomized Placebo-Controlled Trial (2026) · cites this paper as [11]
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Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF)
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Self-citation
- Authors
- Chen, M. C., Korth, C. C., Harnett, M. D., Elenko, E., & Lickliter, J. D.
- Affiliations
- PureTech Health Boston Massachusetts USA
- PureTech (United States) (US)
- Nucleus Network Melbourne Australia
- Venue
- Clinical Pharmacology in Drug Development
- Publisher
- Wiley
- Published
- 2021-11-15
- Volume
- 11
- Issue
- 2
- Pages
- 220-234
- ISSN
- 2160-763X (ISSN-L)
- 2160-7648
- OpenAlex
- W3212147235
- Cited by
- 18
- References
- 29
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology in Drug Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Keywords
- interstitial lung disease, antifibrotic agents, fibrotic diseases, pharmacokinetics, food effect, safety and tolerability, maximum tolerated dose, dose proportionality, drug metabolism, adverse events
- MeSH terms
- Deuterium, Dose-Response Relationship, Drug, Humans, Pyridones, Lung Diseases, Interstitial
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