navafenterol (AZD8871) / AstraZeneca, Almirall - LARVOL DELTA

Experimental drugs in clinical trials for COPD: Artificial Intelligence via Machine Learning approach to predict the successful advance from early-stage development to approval. (PubMed, Expert Opin Investig Drugs) - "Different ML models, trained from prior knowledge on clinical trial success, were used to predict the probability that experimental drugs will successfully advance toward approval in COPD, according to Bayesian inference as follows: ≤25% low probability, >25% and ≤ 50% moderate probability, >50% and ≤ 75% high probability, and > 75% very high probability. The Artificial Neural Network and Random Forest ML models indicated that, among the current experimental drugs in clinical trials for COPD, only the bifunctional muscarinic antagonist - β-adrenoceptor agonists (MABA) navafenterol and batefenterol, the inhaled corticosteroid (ICS)/MABA fluticasone furoate/batefenterol, and the bifunctional phosphodiesterase (PDE) 3/4 inhibitor ensifentrine resulted to have a moderate to very high probability of being approved in the next future, however not before 2025."

Journal • Machine learning • Review • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Navafenterol for chronic obstructive pulmonary disease therapy. (PubMed, Expert Opin Investig Drugs) - "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."

Journal • Chronic Obstructive Pulmonary Disease • Cough • Immunology • Pulmonary Disease • Respiratory Diseases

The Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and β Adrenergic Receptor Agonist Navafenterol in Human Small Airways. (PubMed, Cells) - "Propranolol completely reversed the inhibitory effect of navafenterol on TxA analog-induced bronchoconstriction. In the presence of histamine or TxA analog, navafenterol exhibits bronchoprotective effect in human airways and it is primarily mediated by βAR agonism of navafenterol."

Journal • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

The novel bronchodilator navafenterol: a phase 2a, multi-centre, randomised, double-blind, placebo-controlled crossover trial in COPD. (PubMed, Eur Respir J) - P2a | "Once-daily navafenterol was well tolerated, improved lung function and reduced COPD-related symptoms, similar to an established once-daily fixed-dose combination bronchodilator."

Clinical • Journal • P2a data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Navafenterol (AZD8871) in healthy volunteers: safety, tolerability and pharmacokinetics of multiple ascending doses of this novel inhaled, long-acting, dual-pharmacology bronchodilator, in two phase I, randomised, single-blind, placebo-controlled studies. (PubMed, Respir Res) - P1 | "Multiple ascending doses of navafenterol were well-tolerated and the safety and pharmacokinetics of navafenterol were similar in non-Japanese and Japanese volunteers. The findings support navafenterol clinical development."

Clinical • Journal • PK/PD data • Asthma • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Navafenterol (AZD8871) in patients with mild asthma: a randomised placebo-controlled phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of this novel inhaled long-acting dual-pharmacology bronchodilator. (PubMed, Respir Res) - P1 | "In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h."

Clinical • Journal • P1 data • PK/PD data • Asthma • Pain • Respiratory Diseases

Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator. (PubMed, Respir Res) - P1 | "Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised."

Clinical • Journal • P1 data • PK/PD data • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

A Randomized Trial of Dual-Acting Bronchodilator AZD8871 for Chronic Obstructive Pulmonary Disease. (PubMed, Am J Respir Crit Care Med) - No abstract available

Clinical • Journal

Pharmacological profile of AZD8871 (LAS191351), a novel inhaled dual M3 receptor antagonist/b2-adrenoceptor agonist molecule with long-lasting effects and favorable safety profile. (PubMed, J Pharmacol Exp Ther) - "AZD8871 exhibits a higher muscarinic component than batefenterol in human bronchi, with a shift in potency under propranolol blockade of 2- and 6-fold, respectively, together with a persisting relaxation (5.3% recovery at 8 hours). Thus, AZD8871 has the potential to be a next generation of inhaled bronchodilators in respiratory diseases. SIGNIFICANCE STATEMENT: N/A."

Clinical • Journal

A Single Inhalation Dose Study to Assess Efficacy, Pharmacokinetics (PK), Safety and Tolerability of AZD8871 in Patients With Long-term Lung Diseases. (clinicaltrials.gov) - P2a; N=73; Completed; Sponsor: AstraZeneca; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Single Inhalation Dose Study to Assess Efficacy, Pharmacokinetics (PK), Safety and Tolerability of AZD8871 in Patients With Long-term Lung Diseases. (clinicaltrials.gov) - P2a; N=73; Active, not recruiting; Sponsor: AstraZeneca; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed