Developmental Progress and Future Potential for Inhaled Biologics in the Treatment of Respiratory Diseases

Abstract

Inhaled biologics to treat lung diseases have an extensive history. This is counterbalanced by the limited products that have reached the commercialization stage of development despite the numerous disease states and targets that may be suitable for the delivery of proteins, peptides, or nucleic acid therapeutics. These opportunities are reviewed alongside current and past clinical and preclinical studies that highlight both successful and discontinued programs, providing key lessons for future development. Although there are physical, biological, and technical barriers that must be overcome to successfully deliver these relatively fragile moieties to the lung, there are commercial and clinical reasons why success has not always been realized. This review captures the current landscape of inhaled biologics, and as the field advances, we expect the inhaled route to expand rapidly given its distinct pharmacokinetic advantages for local lung diseases.

Introduction

Understanding the future potential for inhaled biologics for the treatment of local lung diseases can be best achieved through reflecting on the past successes, failures, and advances made in the science and technology of inhaled biologics. Certainly, many candidate biologics (defined here as proteins, peptides, or nucleic acids) have been identified for treating a wide range of lung diseases. Through these product development efforts, our understanding of the barriers to developing these molecules has improved substantially, including physicochemical, physiological, pharmacological, and commercial challenges.

Inhaled biologics represent a complex therapeutic modality, and because of the complex molecular limitations of the active pharmaceutical ingredient (API), one must be especially careful to integrate formulation design, processing, aerosolization, deposition, and the subsequent distribution/release events in the lung environment. Feasibility is contingent on ensuring that the biologic remains stable throughout manufacturing, storage, and delivery, that excipients are acceptable for inhalation, and that the target dose can be efficiently administered to and deposited at the disease site in the respiratory tract. As evident from the clinical inhaled biologic programs described below, delivery of the biologic to the lung alone does not guarantee success. Disease complexity and commercial factors must also be considered. With this in mind, we review those local lung disease states with potential targets for inhaled biological therapeutics. We then provide an up-to-date inventory of biologics that were/are in clinical studies. These include ongoing trials, programs that did not progress, and approved therapeutics. This retrospective analysis is used to identify key challenges specific to inhaled biologics, including stability, immunogenicity, formulation–device integration, manufacturing, dose requirements, pulmonary physiological barriers, and pharmacokinetic assessment, and to review strategies for overcoming these barriers to enable successful clinical translation.

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2 Inhaled Biologics in the Clinic

The successful development of inhaled biologics is influenced by multiple factors. As of 2025, there are five biologics for treating respiratory diseases approved for direct delivery to the human airways: two from the US FDA, one from Japan’s PMDA, one from China’s NMPA, and one from India’s CDSCO [1,2,3,4,5]. There is a growing pipeline of investigational proteins at various stages of development, including recombinant proteins, non-recombinant proteins, and antibody fragments. As for delivery devices, most candidates have been formulated for nebulization, while the others utilize dry powder inhaler (DPI) systems. Inhalable biologics in development are summarized in Table 1.

Abstract of Table 1: Clinical studies of inhaled biologics

Giri, B.R., Spahn, J.E., Alsaidalani, R. et al. Developmental Progress and Future Potential for Inhaled Biologics in the Treatment of Respiratory Diseases. Drugs (2026). https://doi.org/10.1007/s40265-026-02336-8

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