TABLE 2

Overview of the major biologic approaches currently in development for type 2 low asthma management

Studied biomarkerBiologicDrug typeSponsorMain effects[Ref.]
Add-on therapy in severe uncontrolled neutrophilic asthmaIL-8SCH527123/navarixinCXCR2 antagonistAstraZenecaReduction in sputum neutrophils and in blood neutrophils
No improvement in clinical outcomes and exacerbation rates
[81–83]
Add-on therapy in uncontrolled moderate-to-severe asthmaIL-17BrodalumabHuman anti-IL-17 receptor A monoclonal antibodyLeo PharmaDid not improve ACQ score, lung function or asthma symptoms[84]
Add-on therapy in severe uncontrolled neutrophilic asthmaPDE4PRL-554 CHF6001 (inhaled)Dual phosphodiesterase PDE3 and PDE4 inhibitorsVerona Pharma, Chiesi FarmaceuticiBronchodilatatory and anti-inflammatory effect[85, 86]
Severe and mild asthma
Severe, refractory, or steroid-resistant asthma
TNF-αEtanercept, golimumabHuman monoclonal antibody against TNF-αPfizer, Janssen BiologicsTreatment was associated with substantial adverse reactions such as infections and malignancies[87, 88]
Add-on therapy in severe uncontrolled neutrophilic asthmaIL-1AnakinraHuman IL-1 receptor antagonistSwedish Orphan BiovitrumReduced neutrophilic airway inflammation and sputum levels of IL-1β, IL-6 and IL-8[89]
Severe neutrophilic asthmap38 MAPK tyrosine kinaseLosmapimod, AZD7624, masitinib, imatinibProtein kinase inhibitors, MAPK inhibitors, tyrosine kinase inhibitorsGlaxoSmithKline, AstraZeneca, AB Science, NovartisReduced exacerbations
Reduced inflammatory biomarkers from blood (IL-6, neutrophil percentage and CRP) and sputum (IL-6 and IL-8)
Improved asthma control
[90–92]
Severe uncontrolled asthma
Severe neutrophilic asthma
PI3-kinaseNemiralisib, IPI-145, RV-1729 (duvelisib)PI3-kinase inhibitorsGlaxoSmithKlineNo discernible difference in trough FEV1 and ACT score
Attenuation of airway inflammation, promotion of bronchodilation and reversal of β2-adrenoreceptor tachyphylaxis
[93–96]

IL: interleukin; ACQ: Asthma Control Questionnaire; PDE: phosophdiesterase; TNF: tumour necrosis factor; MAPK: mitogen-activated protein kinase; CRP: C-reactive protein; PI3: phosphoinositide 3; FEV1: forced expiratory volume in 1 s; ACT: Asthma Control Test.