Cyclosporine formulations for use in the treatment of bronchiolitis obliterans syndrome (BOS)
Inventors
IACONO, ALDO • Denk, Oliver • Boerner, Gerhard
Assignees
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Publication Number
US-12178843-B2
Publication Date
2024-12-31
Expiration Date
Abstract
The present invention relates to a composition comprising cyclosporine A (CsA) for use in the prevention of bronchiolitis obliterans syndrome (BOS) in a double lung transplanted patient, or for the treatment of BOS or for the prevention or delay of the progression of BOS in a double lung transplanted patient being diagnosed with BOS, wherein the composition is administered to said patient by inhalation of said composition in aerosolized form comprising a therapeutically effective dose of cyclo-sporine A.
Core Innovation
The invention provides a method for treating bronchiolitis obliterans syndrome (BOS) in a double lung transplanted patient, or for delaying the onset or progression of BOS in a double lung transplanted patient being diagnosed with BOS. The method administers, by inhalation, a composition comprising liposomal cyclosporine A (L-CsA) in aerosolized form containing a therapeutically effective dose of cyclosporine A.
The aerosolized composition is based on liposomal cyclosporine A (L-CsA) formulated for inhalation. The liposome characteristics are described as unilamellar with an average particle size on the order of about 40–100 nm and a low polydispersity index, and the formulation includes lecithin/phospholipids, polysorbate 80, and an aqueous saline vehicle.
Delivery is characterized by aerosol and inhalation performance, including in vitro aerosol characterization and drug delivery via nebulizer options such as an electronic vibrating membrane nebulizer and eFlow® nebulizer. Documented performance endpoints include BOS definitions and grading, forced expiratory volume in one second (FEV1) decline criteria, event-free survival probabilities, and overall survival, including comparative outcomes versus standard of care (SOC) alone.
Claims Coverage
The partial content identifies one independent claim directed to inhaled aerosolized liposomal cyclosporine A for treating or delaying bronchiolitis obliterans syndrome (BOS) in a double lung transplanted patient. The associated dependent claims refine the delivery, patient management constraints, and measurable clinical performance endpoints, including FEV1-based thresholds, event-free survival probability and event definitions, inhalation adherence, and vehicle/formulation constraints.
Inhaled aerosolized liposomal cyclosporine A for BOS in double lung transplanted patients
Administering to a double lung transplanted patient, by inhalation, an aerosolized composition comprising liposomal cyclosporine A (L-CsA) in a therapeutically effective dose of cyclosporine A, for treating BOS or delaying onset or progression of BOS.
Limiting FEV1 decline to delay or reduce BOS progression
Reducing onset or progression of BOS by limiting the patient’s forced expiratory volume in one second (FEV1) decline to up to 20% relative to the FEV1 value at the beginning of treatment.
Event-free survival probability endpoint with defined events
Requiring that a double lung transplant patient diagnosed with BOS has an event-free survival probability of at least 60% after at least 48 weeks from the start of treatment, where an event includes less than or equal to 20% FEV1 decline, re-transplantation, and/or death.
Electronic vibrating membrane nebulizer aerosolization
Aerosolizing the composition using an electronic vibrating membrane nebulizer.
Inhalation adherence threshold
Including inhaling the composition such that adherence is at least 75%.
Saline aqueous liquid vehicle
Specifying that the aqueous liquid vehicle essentially consists of saline.
Across the identified independent claim and refinements, the core coverage centers on inhalation of an aerosolized therapeutically effective dose of cyclosporine A delivered as liposomal cyclosporine A (L-CsA) for BOS in double lung transplanted patients, with further constraints based on FEV1 decline, event-free survival probability after a defined treatment duration, nebulizer type, inhalation adherence, and an essentially saline aqueous vehicle.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating bronchiolitis obliterans syndrome (BOS) in a double lung transplanted patient by administering inhaled aerosolized liposomal cyclosporine A (L-CsA).
Delaying the onset or progression of BOS in a double lung transplanted patient being diagnosed with BOS by administering inhaled aerosolized liposomal cyclosporine A (L-CsA).
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