Cyclosporine formulations for use in the treatment of bronchiolitis obliterans syndrome (BOS)

Inventors

IACONO, ALDO • Denk, Oliver • Boerner, Gerhard

Assignees

Breath Therapeutics GmbH

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 cyclosporine A.

Core Innovation

The invention relates to compositions and a dosing strategy for aerosolised liposomal cyclosporin A (L-CsA) for treating bronchiolitis obliterans syndrome (BOS) or delaying the progression of BOS in double lung transplanted patients. The approach identifies double lung transplanted patients who are at risk to develop or subsequently have developed BOS and administers a therapeutically effective dose of aerosolised L-CsA by inhalation.

A key feature is the use of an inhaled aerosol formulation of liposomal cyclosporin A (L-CsA), including phospholipids/lecithin, a non-ionic surfactant such as polysorbate 80, and unilamellar liposomes in a size range of about 40–100 nm, with reconstitution in a saline vehicle. The formulation is characterized by physical properties including osmolality and vehicle conditions as described.

Clinical rationale and efficacy are evaluated using FEV1-based BOS definitions, grading, and event-free survival metrics over treatment periods within the first 48 weeks. The document reports comparative outcomes versus standard immunosuppressive therapy (SOC), including Kaplan–Meier event-free survival comparisons and FEV1 stabilization trends for double lung L-CsA versus decline with SOC, including reported values and hazard ratio comparisons.

Claims Coverage

The partial claims include two independent claims. Each independent claim defines a method that identifies double lung transplanted patients diagnosed with BOS (or at risk) and administers aerosolised liposomal cyclosporin A (L-CsA) by inhalation, with quantitative constraints based on FEV1 change within the first 48 weeks.

Across the independent claims, the inventive concept is directed to administering aerosolised liposomal cyclosporin A (L-CsA) by inhalation to double lung transplanted patients who are diagnosed with BOS (or at risk), while maintaining quantitative lung function constraints based on FEV1 change during the first 48 weeks.

Stated Advantages

Documented Applications