Will pulmonary drug delivery for systemic application ever fulfill its rich promise?

Figures & data

Figure 1. Improved Inhalation Technologies like AERx lead to Reduced Inter-subject Variability and Greater Lung Deposition. Yellow circles are for AERx, green triangles are for DPIs, blue diamonds are for MDIs and red squares are for nebulizers. Adapted with permission from Cipolla D et al., [8]. Copyright 2010 Future Science. Full colour available online

Figure 2. Systemic Absorption of Peptides and Proteins from the Lung. Following intratracheal instillation in rats and dogs, the bioavailability relative to SC injection and the Tmax are reported. Adapted from [2].

Table 1. Systemic inhaled products in development to treat patient populations with unmet needs.

Unmet need	Drug	Product and latest stage of development	Manufacturer	Reference
T2D not on injectable insulin	Insulin	Afrezza, marketed	MannKind	[11–13]
		AERx iDMS, Phase 3	Aradigm	[7,13]
		Dance-501, Phase 2	Dance Biopharm	[13]
Anxiety^a	Loxapine	Adasuve, marketed	Alexza Pharma	[1,13]
Migraine^b	Dihydroergotamine	Semprana, NDA submission	Allergan	[1,13]
	Zolmitriptan	CVT-427, Phase 1	Acorda Ther.	-
Parkinson’s disease	Levodopa	CVT-301, Phase 3	Acorda Ther.	[13]
Breakthrough pain management	Morphine/fentanyl	AERx PMS, Phase 2	Aradigm	[1,7,13]
Smoking cessation	Nicotine	AERx nicotine, Phase 2	Aradigm	[1,7,13,16]
Insomnia	Zaleplon	AZ-007, preclinical	Alexza Pharma	[1]
Acute coronary syndrome	Relaxin	Unavailable	Unavailable	–
Idiopathic pulmonary fibrosis	IFNγ	Preclinical	InspirRx Pharma/Nostrum Pharm	[1,13]

^aDue to risk evaluation and mitigation strategies, the marketing restrictions with this product make it difficult to address the true unmet need in bipolar disorder and schizophrenia.

^bSemprana was formerly named Levadex; NDA: new drug application; PMS: pain management system.

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