CHF 6523 / Chiesi - LARVOL DELTA

How to Design an Inhaled Drug: CHF-6523. (PubMed, J Med Chem) - "The appearance of a successful campaign delivering an inhaled PI3Kδ inhibitor is therefore an opportunity to highlight how a team can address the challenges involved in the identification of such a compound. This Viewpoint seeks to highlight a great example of medicinal chemistry in the inhaled space."

Journal • PIK3CD

Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease. (PubMed, J Med Chem) - "This novel inhaled selective PI3Kδ inhibitor displayed durable anti-inflammatory activity in a disease-relevant rat model of Th-2-driven acute lung inflammation and safe in vitro and in vivo preclinical profiles. Therefore, compound 18 showed the appropriate discovery profile and was progressed to clinical trials in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients as CHF-6523."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • PIK3CD

CHF6523 data suggest that the phosphoinositide 3-kinase delta isoform is not a suitable target for the management of COPD. (PubMed, Respir Res) - P1 | "These data, together with those from other PI3K inhibitors, suggest that PI3Kδ is not a suitable pathway for the management of COPD, as the achieved target engagement did not translate into any pharmacodynamic anti-inflammatory effect."

Clinical • Journal • Chronic Obstructive Pulmonary Disease • Cough • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • PIK3CD

Animal models to assess potential post-inhalation irritant effects associated with inhaled drugs. (ERS 2024) - "To validate the assay, rats or guinea-pigs were exposed to a series of inhaled compounds (AZD9164, CHF6523 and Nemiralisib) given as dry powder that induced drop in FEV1 or cough as adverse event in humans. No effect was observed with BDP. These data demonstrate that it is possible to assess the potential irritant effects associated with inhaled drugs using a head-out plethysmography applied to the inhalation system, thus helping in the selection of molecules devoid of such effects."

Preclinical • Cough • Inflammation • Respiratory Diseases

Investigate the Safety, Tolerability and Pharmacokinetics of CHF6523 in Healthy and in COPD Subjects (clinicaltrials.gov) - P1 | N=136 | Completed | Sponsor: Chiesi Farmaceutici S.p.A. | Recruiting ➔ Completed | N=102 ➔ 136

Enrollment change • Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Investigate the Safety, Tolerability and Pharmacokinetics of CHF6523 in Healthy and in COPD Subjects (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Trial completion date: Jul 2022 ➔ Dec 2022 | Trial primary completion date: Jul 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Investigate the Safety, Tolerability and Pharmacokinetics of CHF6523 in Healthy and in COPD Subjects (clinicaltrials.gov) - P1; N=102; Recruiting; Sponsor: Chiesi Farmaceutici S.p.A.; Trial completion date: Dec 2020 ➔ Jul 2022; Trial primary completion date: Dec 2020 ➔ Jul 2022

Clinical • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases