Navafenterol for chronic obstructive pulmonary disease therapy

ABSTRACT

Introduction

Chronic obstructive pulmonary disease (COPD) is a prevalent disease of the airways in which inhaled bronchodilators can be given as monotherapy or fixed dose combination, in order to better control disease symptoms and to reduce its morbidity. A novel bronchodilator approach is represented by bifunctional molecules such as navafenterol, which exert dual synergic bronchodilator effects as a monotherapy. Navafenterol is currently being investigated for COPD.

Areas covered

This review summarizes the preclinical data regarding navafenterol synthesis and in vitro and in vivo testing. Clinical data coming from phase I and II studies are also discussed. Navafenterol was found to improve lung function, dyspnea, and cough severity and was well tolerated, and its effect was comparable with that of fixed-dose combinations in patients with moderate-to-severe COPD.

Expert opinion

Despite clinical evidence of efficacy for navafenterol is still limited, the existing data prompts further clinical evaluation and also consideration of other inhalation approaches such as pressure metered-dose inhalers (pMDIs) or nebulization. Other interesting approach would be combination with another bifunctional molecule such as ensifentrine.

KEYWORDS:

• Aclidinium
• formoterol- bronchodilators-chronic obstructive pulmonary disease-glycopyrrolate
• formoterol-indacaterol
• glycopyrrolate-muscarinic antagonist beta 2 agonist (MABA)-navafenterol- tiotropium
• olodaterol

Article highlights

• COPD is a prevalent disease of the airways in which inhaled bronchodilators can be given as monotherapy or as fixed dose combinations

• Fixed dose combination has the advantage of a more potent effect over the individual components due to the synergism in the mechanisms of action

• Similar effects can be obtained more recently with bifunctional molecules with both antimuscarinic and beta2 agonist effects (MABA) monotherapy

• Navafenterol is such a MABA currently evaluated as a dry powder formulation for inhalation in COPD

• Navafenterol improved lung function, reduced the burden of respiratory symptoms and was well tolerated

• Navafenterol could also be formulated for nebulization or in combination with other bifunctional molecules, such as ensifentrine.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

A reviewer on this manuscript has disclosed that they serve as a consultant for AstraZeneca on trials. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.