Methods and compositions for treatment of pulmonary hypertension and other lung disorders

Inventors

Weers, Jeffry • ROMERO, ALAIN • SMYTH, HUGH • Curtis, Robert • FROST, Adaani • Xu, Zhen • Shreeniwas, Revati • Donovan, Martin

Assignees

Respira Therapeutics Inc

Abstract

Provided herein are methods for treating pulmonary hypertension. The methods include administering to a subject in need thereof an effective amount of a vasodilator, wherein the vasodilator is administered to the subject via inhalation pro re nata using a portable inhaler. In some embodiments, the vasodilator is a PDE5 inhibitor. Pharmaceutical compositions for pro re nata administration of vasodilators are also described.

Core Innovation

The invention concerns a method of treating pulmonary hypertension by administering, to a subject in need thereof, an effective amount of a pharmaceutical carrier-based composition comprising about 0.1% to about 10% vardenafil or salts or hydrates thereof relative to the total weight of the composition, and a powder base. The vasodilator is administered to the subject via inhalation pro re nata at least 2-30 minutes before physical exertion using a portable inhaler.

The invention is positioned to address pulmonary vascular dysfunction by delivering a vasodilator lung-targeted formulation intended to avoid systemic side effects and to reduce ventilation/perfusion mismatch. The disclosed patient groups include pulmonary arterial hypertension (PAH) (WHO Group 1) and pulmonary disease-related pulmonary hypertension including WHO Group 3 and WHO Group 4 (CTEPH), and the disclosed clinical context includes evaluation parameters such as right heart catheterization measures, cardiac output, and functional outcomes.

A further aspect is the use of carrier-based dry powder formulations for inhalation with measurable delivery performance, including fine particle fraction and total lung dose. Formulation embodiments include micronized vardenafil with a carrier such as lactose, optionally with a force control agent selected from magnesium stearate and leucine, and the invention also contemplates combination therapy with a second inhaled drug such as a soluble guanylate cyclase stimulator and optionally bronchodilators.

The detailed disclosures include powder-base composition options and inhaler/device concepts using a portable inhaler, including dry powder inhaler concepts, together with characterization and testing frameworks for aerosol performance and patient use timing. The document also describes manufacture and aerosol testing examples for vardenafil/lactose blends, and it specifies quantitative formulation and aerosol performance metrics such as MMAD, Dv50, emitted dose, fine particle dose, and dose-related targets.

Claims Coverage

The claims coverage includes one independent method claim, with multiple dependent claims refining formulation composition, inhalation performance, device type, dosing-related constraints, and optional combination therapy. The independent claim is grounded on administering a vardenafil-containing carrier-based powder composition via inhalation pro re nata using a portable inhaler shortly before physical exertion.

Overall, the claim set centers on PRN inhalation treatment of pulmonary hypertension using a portable inhaler with a carrier-based powder composition containing vardenafil, and it further refines the approach with specific formulation composition, inhalation performance, device type, and optional co-therapy via an sGC stimulator plus force-control excipient options.

Stated Advantages

Documented Applications