Table 4.
Selected clinical studies and marketed products of inhaled biologic therapy.
| Name | API | Development Stage | Company/Sponsor | Clinical Application | Delivery Device | Formulation | Reference, Year & Clinical Trial Number |
|---|---|---|---|---|---|---|---|
| Inhaled proteins | |||||||
| Afrezza® | Insulin, 5.7 kDa | Marketed in 2014 | MannKind | Diabetes mellitus | Dreamboat® inhaler | Technosphere® insulin inhalation powder | [187,188] 2014 |
| Alpha-1 HC | Human α1-PI, 52 kDa | Phase II | Grifols Therapeutics | CF | AKITA2 APIXNEB® nebuliser system | Inhaled solution | [158] 2016, NCT01684410 |
| AZD1402/PRS-060 | IL4 mutein (IL-4Rα antagonist), ~18 kDa | Phase I | AstraZeneca & Pieris Pharmaceuticals | Asthma | InnoSpire Go mesh nebuliser | Inhaled solution | [164,165] 2019, NCT03384290 and NCT03574805 |
| Alteplase | rt-PA, 70 kDa | Phase II | University of Michigan & Genentech | Acute plastic Bronchitis | Nebuliser | Inhaled solution | [175] 2017, NCT02315898 |
| ALX-009 | OSCN-/bLF, 80 kDa | Phase I | Alaxia SAS | P. aeruginosa and Bcc infection in CF | Nebuliser | Inhaled solution | [174] 2018, NCT02598999 |
| Alidornase alfa (PRX-110, AIR Dnase™) | rhDNase I, 37 kDa | Phase I | Protalix | CF | Philips Respironics I-neb AAD inhaler system | Inhaled solution | [155] 2017, NCT02605590 |
| Dornase alfa (Pulmozyme®) | rhDNase I, 37 kDa | Marketed in 1993 | Genentech | CF | Jet nebuliser/air compressor combinations | Inhaled solution | [189] 1996 |
| Dornase alfa | rhDNase I, 37 kDa | Phase IV | Erasmus Medical Centre-Sophia Children’s Hospital | CF | AKITA2 APIXNEB® nebuliser system | Inhaled solution | [128] 2011 |
| Dornase alfa | rhDNase I, 37 kDa | Phase IV | PARI | CF | eRapid™ nebuliser system | Inhaled solution | [124] 2015, NCT01712334 |
| DAS181 (Fludase®) | Recombinant sialidase fusion protein, 46 kDa | Phase I/II | Ansun BioPharma | Parainfluenza infection | Cyclohaler® DPI | Dry powder | [154,167] 2015, NCT01037205, NCT01924793 NCT01113034 |
| Compassionate use/Phase III | Renmin Hospital of Wuhan University & Ansun BioPharma | COVID-19 | Nebuliser | Inhaled solution |
NCT04324489 NCT03808922 |
||
| Exubera® | Insulin, 5.7 kDa | Marketed in 2006; withdrawn in 2007 | Pfizer/Nektar Therapeutics | Diabetes mellitus | Exubera® DPI inhaler | SD powder | [190] 2004 |
| EpoFc | Epo Fc-fusion protein | Phase I | Syntonix Pharmaceuticals | Anemia | Aeroneb® Pro nebuliser | Inhaled solution | [117] 2005 |
| GM-CSF (Leukine®, Sargramostim) | rhuGM-CSF, 14 kDa | Phase I | Milton S. Hershey Medical Center | RASP | Nebuliser | Inhaled solution | NCT02601365 |
| Phase II | Children’s Hospital Medical Center, Cincinnati | PAP | Nebuliser | Inhaled solution | NCT01511068 | ||
| Phase II | Peking Union Medical College Hospital | PAP | Nebuliser | Inhaled solution | NCT02243228 | ||
| Kamada AAT | Alpha-1-antitrypsin, 52 kDa | Phase II | Kamada | CF | PARI eFlow® nebuliser | Inhaled solution | [160] 2009 |
| Kamada-API | Alpha-1-antitrypsin, 52 kDa | Phase II/III | Kamada | AATD | PARI eFlow® nebuliser | Inhaled solution | [161] 2017, NCT04204252 |
| Pitrakinra (Aerovant®, AER-001) | IL4 mutein (IL-4Rα antagonist), 15 kDa | Phase II | Bayer | Asthma | PARI LC Plus nebuliser | Inhaled solution | [163] 2007, NCT00535031 |
| Aldesleukin (Proleukin®) | Recombinant IL-2, 15 kDa | Phase I/II | M.D. Anderson Cancer Center | Lung metastases | Nebuliser | Inhaled solution | [173] 2000, NCT01590069 |
| Survanta® | Bovine surfactant (phospholipids, triglycerides, free fatty acids and proteins, etc.) | Phase I/II | DMC Foundation | RDS | MiniHeart jet nebuliser | Inhaled solution | [191] 2019, NCT02294630 |
| SNG001 | Interferon-beta 1a, 22 kDa | Phase II | Synairgen | RVI in asthma | Nebuliser | Inhaled solution | [168,170] 2014, NCT01126177 |
| Phase II | Synairgen | COPD | Nebuliser | Inhaled solution | [169] 2019 | ||
| Phase II | Synairgen | COVID-19 | Nebuliser | Inhaled solution | [171] 2020, NCT04385095 |
||
| Inhaled mAbs and mAb fragments | |||||||
| ALX-0171 | Anti-F protein trivalent Nanobody®, 42 kDa | Phase II | Ablynx | RSV infection | FOX-Flamingo inhalation system | Inhaled solution | 2017, NCT02979431 and NCT03418571 |
| CSJ117 | Anti-TSLP antibody fragment, 46 kDa | Phase I/II | Novartis | Asthma | Concept1 device (single dose DPI) |
PulmoSol™ engineered powder | [181] 2020, NCT03138811 and NCT04410523 |
| E25 | Omalizumab, 149 kDa | Phase III | Genentech/Novartis | Asthma | PARI IS-2 nebuliser | Inhaled solution | [35] 1999 |
| GSK1995057 | Anti-TNFR1 dAb, 13 kDa | Phase I | GSK | Acute lung injury | PARI eFlow® nebuliser | Inhaled solution | [38] 2018, NCT01587807 |
| GSK2862277 | Anti-TNFR1 dAb, 13 kDa | Phase II | GSK | Postoperative lung injury | PARI eFlow® nebuliser | Inhaled solution | [93] 2020, NCT02221037 |
| VR942/ CDP7766 | Anti-IL-13 mAb fragment | Phase I | UCB Pharma | Asthma | Multidose F1P DPI | Dry powder | [45] 2018, NCT02473939 |
API: active pharmaceutical ingredient; AAT: alpha-1-antitrypsin; AATD: alpha-1-antitrypsin deficiency; bLF: bovine lactoferrin; Bcc: burkholderia cepacia complex; CF: cystic fibrosis; COPD: Chronic obstructive pulmonary disease; dAb: domain antibody; DPI: dry powder inhaler; Epo: erythropoietin; RDS: respiratory distress syndrome; RSV: respiratory syncytial virus; rhDNase I: recombinant human deoxyribonuclease I; IL-2: interlukin-2; OSCN-: Hypothiocyanite; PAP: pulmonary alveolar proteinosis; P. aeruginosa: pseudomonas aeruginosa; rt-PA: recombinant tissue plasminogen; rhuGM-CSF: recombinant human granulocyte-macrophage colony stimulating factor; RASP: respiratory virus-associated severe pneumonia; RVI: respiratory viral infection; SD: spray dried; TNFR1: tumour necrosis factor receptor-1; IL-4Rα: interleukin-4 receptor alpha; IL-13: interleukin-13; PI: protease inhibitor; TSLP: thymic stromal lymphopoietin.