Table 3 Development of other drugs for COPD

Bimosiamose

A synthetic pan-selectin antagonist that targets E-, P- and L-selectin. In vitro, bimosiamose blocks adhesion of neutrophils

Bimosiamose (TBC 1269) was in Phase II for treatment of asthma(inhaled), reperfusion injury (injectible) and psoriasis (topical). There was an additional inhaled version of TBC 1269 in preclinical investigation for asthma. Revotar Ag (Germany) under a license from Encysive is continuing development of an inhaled version of TBC 1269 for asthma and COPD and a cream and subcutaneous administration for psorias (NCT01108913).

²⁵⁵

Eleuquin (EL246)

Anti-E/L-selectin monoclonal antibody, which recognises specific positions on the E and L selectins to inhibit cell adhesion.

EL246 (Eleuquin) is under predevelopment by LigoCyte for the treatment of acute inflammatory conditions such as COPD, ischaemic reperfusion injury and transplant reject.

¹⁷⁷

BIBW 2948

Reduce internalisation of EGFR

Inhalation of BIBW 2948 (4 weeks) reduced internalisation of EGFR but did not reduce mucin stores (NCT00423137).

¹⁷⁹

PDE4 inhibiotr

Inhibit PDE4 and increase cAMP levels in inflammatory cells, regulating the activity of inflammatory cells, and regulating the release of inflammatory factors to exhibit anti-inflammatory effects

Roflumilast has been approved by the Food and Drug Administration (FDA) as a COPD treatment. Roflumilast relieves the symptoms of dyspnoea in COPD patients and reduces the frequency of acute attacks, but has side effects such as nausea, vomiting, and headache. GSK-256066 (4-week inhaled treatment) in DBPCRT (NCT00549679) improved residual volume and showed no significant trend of FEV1 after bronchodilator. CHF6001 is in clinical testing (28-day treatment) (NCT01730404) but no results have been reported. The others are in clinical testing, such as, MK-0359 (NCT00482235); MK-0873 (NCT00132730); tofimilast (NCT00219622); UK-500,001 (NCT00263874); tetomilast (OPC-6535) (NCT00874497), terminated, (NCT00917150); oglemilast (NCT00671073); QAK423A (NCT01197287); and TPI 1100 (NCT00914433).

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Bosentan

Blocks endothelin receptor.

Bosentan (18 months) can alleviate the condition of COPD patients and prevent the progression of pulmonary hypertension. This effect is more significant in GOLD III and IV patients. But for COPD patients without pulmonary hypertension, bosentan will aggravate their hypoxaemia.

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Solithromycin

Decrease the production of proinflammatory cytokines and chemokines by epithelial and immune cells

A macrolide antibiotic. No data of Solithromycin (28 days) collected for this Outcome due to early termination of the trial (NCT02628769)

³³⁹

PPAR agonists

Regulates function of multiple cells of the immune system.

PPARγ agonists includes Troglitazone, Rosiglitazone, and Pioglitazone. PPARα agonists includes Clofibrate and Fenofibrate. Patients who took more than two thiazolidinediones (97.1% rosiglitazone) had significantly less COPD deterioration than patients receiving other diabetes drugs. Results information of clinical trail (February, 10 months) has been submitted to ClinicalTrials.gov by the sponsor or investigator, but is not yet publicly available on ClinicalTrials.gov (NCT00103922)

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