Aerosol pirfenidone and pyridone analog compounds and uses thereof
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Publication Number
US-12226407-B2
Publication Date
2025-02-18
Expiration Date
Abstract
Disclosed herein are formulations of pirfenidone or pyridone analog compounds for aerosolization and use of such formulations for aerosol administration of pirfenidone or pyridone analog compounds for the prevention or treatment of various fibrotic and inflammatory diseases, including disease associated with the lung, heart, kidney, liver, eye and central nervous system. In some embodiments, pirfenidone or pyridone analog compound formulations and delivery options described herein allow for efficacious local delivery of pirfenidone or pyridone analog compound. Compositions include all formulations, kits, and device combinations described herein. Methods include inhalation procedures, indications and manufacturing processes for production and use of the compositions described.
Core Innovation
The invention provides a unit dose of an aqueous solution for delivery by a liquid nebulizer for the daily treatment of interstitial lung disease in an adult human. The unit dose includes a respirable delivered dose comprising water and pirfenidone at a concentration from about 5.0 mg/mL to about 20 mg/mL, and the aqueous solution has an osmolality of from about 50 mOsmol/kg to about 2000 mOsmol/kg.
The respirable delivered dose to lungs of the adult human per day is less than 1.933 mg/kg/day of pirfenidone. This constraint is used to reduce a decline in forced vital capacity (FVC) in the lung of the adult human.
Dependent aspects specify formulation elements such as salts and optional buffers, as well as aerosol or delivery-performance characteristics and pharmacokinetic relationships relative to an 801 mg oral pirfenidone comparator, including blood AUC0-24 constraints.
Claims Coverage
The claim set covers a daily liquid nebulizer unit dose of an aqueous pirfenidone solution for adult interstitial lung disease treatment, with inventive features centered on formulation parameters, lung delivery constraints, and reduction of decline in forced vital capacity (FVC). Dependent claims further refine the aerosol/deposition characteristics, excipient composition, and pharmacokinetic thresholds versus an 801 mg oral comparator.
Aqueous unit dose with pirfenidone concentration and osmolality
A unit dose of an aqueous solution comprising water and pirfenidone at a concentration from about 5.0 mg/mL to about 20 mg/mL, where the aqueous solution has an osmolality of from about 50 mOsmol/kg to about 2000 mOsmol/kg.
Liquid nebulizer delivery for daily interstitial lung disease treatment
Delivery by a liquid nebulizer for the daily treatment of interstitial lung disease in an adult human, comprising a respirable delivered dose.
Reduced per-day lung pirfenidone to reduce FVC decline
The respirable delivered dose to lungs of the adult human per day is less than 1.933 mg/kg/day of pirfenidone to reduce a decline in forced vital capacity (FVC) in the lung of the adult human.
Lung deposition and aerosol characteristic constraints
The liquid nebulizer delivers pirfenidone to the human lung with at least 5% lung deposition and requires multiple defined aerosol characteristics, including droplet size ranges (MMAD/VMD), droplet distribution variability (GSD), fine particle fraction, output rate, and/or the proportion of aqueous solution delivered.
Salt and buffer formulation constraints for the aqueous respirable delivered dose
Each respirable delivered dose is formulated as an aqueous solution containing water and 0.01%–2.0% by weight salts, optionally a phosphate or citrate buffer keeping pH below 8, and having osmolality of 50–2000 mOsmol/kg.
Pharmacokinetic threshold versus an 801 mg oral comparator
The adult human blood AUC0-24 after each respirable delivered dose to the lungs is less than or equivalent to the blood AUC0-24 after an 801 mg oral dose.
Overall, the claim coverage is directed to delivering pirfenidone as an aqueous solution via a liquid nebulizer in a daily unit dose for adult interstitial lung disease, while constraining pirfenidone concentration, solution osmolality, and the per-day amount of pirfenidone delivered to the lungs to reduce decline in forced vital capacity (FVC). Dependent coverage further adds formulation constituents, aerosol/deposition performance constraints, and pharmacokinetic constraints versus an 801 mg oral comparator.
Stated Advantages
Reduces a decline in forced vital capacity (FVC) in the adult human.
Reduce a decline in forced vital capacity (FVC) in the lung of the adult human.
Improved tolerability by reducing risks associated with oral therapy, including GI adverse events, liver function abnormalities, and photosensitivity/phototoxicity.
Documented Applications
Daily treatment of interstitial lung disease in an adult human using a liquid nebulizer delivered aqueous pirfenidone unit dose.
Daily treatment of interstitial lung disease in an adult human, including reducing decline in forced vital capacity (FVC).
Treatment and/or prevention of fibrotic and inflammatory diseases across organs, including pulmonary fibrosis and interstitial lung disease (including idiopathic pulmonary fibrosis).
Treatment and/or prevention of COPD, asthma, pulmonary hypertension, and lung cancer (tumor stroma).
Treatment and/or prevention of extrapulmonary fibrosis affecting heart/kidney/liver.
Treatment of neurologic disease such as multiple sclerosis.
Reducing decline in forced vital capacity (FVC) in the lung of the adult human with interstitial lung disease.
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