Tudorza (aclidinium bromide) / Almirall, Azurity Pharma - LARVOL DELTA

SAVING THE SECOND PUFF: THE PREVALENCE OF PROPER TWO-PUFFS INHALER TECHNIQUE AMONG COPD PATIENTS: A BACK-TO-BASICS REMINDER OF A POTENTIAL RISK FACTOR IN POOR DISEASE CONTROL (CHEST 2025) - "Inhaler devices were identified as HFA, Respiclick, Ellipta, Diskus, Aerosphere, Pressair, Respimat, Handihaler... The ever-increasing armament of inhaler devices for COPD management has expanded our knowledge and ability to help our patients in terms of Quality of Life (QOL) with symptom management and avoidance of hospitalization. This limited but focused study on the fundamental concepts of inhaler technique among patients on 2 puffs inhaler regimen highlights the importance of inhaler device handling education and the potential for poor quality care due to a lack of spacing (30-60 seconds), breath-holding and shaking the inhaler between the first and second puffs. This may be a potential silent risk factor in developing a full-blown COPD exacerbation due to pharmacokinetic factors (lack of drug absorption and medicine- propellant mixture readiness) CLINICAL IMPLICATIONS: 1."

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

Inflammation, lung function, symptoms and reliever use in chronic obstructive pulmonary disease (ERS 2025) - P=N/A | "Participants were switched to maintenance aclidinium bromide 340 μg/formoterol fumarate 12 μg (BID) and reliever salbutamol (100 μg/puff)... Increased inflammation, worsening symptoms and increased reliever use were associated with exacerbation, EXACT and CompEx events. Findings suggest a potential role for anti-inflammatory treatment to prevent COPD exacerbations."

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

Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression. (PubMed, Cell Metab) - "Moreover, aclidinium bromide, an FDA-approved drug, exhibited significant inhibitory effects on CERS3 activity, suggesting its potential application in CRC treatment. These findings elucidate the metabolic pathways and mechanisms underlying ceramide's impact on CRC, highlighting that targeting CERS3 inhibition represents a promising therapeutic strategy for CRC."

Journal • Colorectal Cancer • Metabolic Disorders • Oncology • Solid Tumor • CERS3 • EGFR

AVANT: Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients (clinicaltrials.gov) - P3 | N=1625 | Completed | Sponsor: AstraZeneca | N=1067 ➔ 1625

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

Effect of non-spherical shape of dry powder aerosol drugs on their airway deposition distribution. (PubMed, Int J Pharm) - "Aerosol particles of Bretaris® Genuair®, Buventol® Easyhaler® and Trelegy® Ellipta® were collected on the stages of a Next Generation Impactor after their emission from the dry powder inhalers...Although there was some inter-drug difference in terms of shape factors, the values were quite close to unity (usually between 1.02 and 1.06), except for the fiber-shaped particles representing a minority in the composition of Trelegy® Ellipta®, which could be characterized by shape factors of around 1.6. The results of computer simulations of deposition distribution indicate that neglecting the irregular shape does not lead to a major distortion of the simulation results unless fiber-shaped particles are also present after the formulation."

Journal

PREVALENCE OF PROPER INHALER PRIMING AND CLEANING AMONG COPD PATIENTS: SILENT RISK FACTORS IN POOR DISEASE CONTROL--A BACK-TO-BASICS REMINDER TO PATIENTS AND HEALTH CARE PROVIDERS (CHEST 2024) - "Inhaler devices were identified as HFA, Respiclick, Ellipta, Diskus, Aerosphere, Pressair, Respimat, Handihaler... The ever-increasing armament of inhaler devices for COPD management has expanded our knowledge and ability to help our patients in terms of Quality of Life (QOL) with symptom management and avoidance of hospitalization. The choices in inhaler devices have also added confusion regarding the optimal use of devices among patients and their providers. This limited."

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

The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants. (PubMed, Int J Chron Obstruct Pulmon Dis) - P1 | "Single and multiple doses of aclidinium were well tolerated in healthy Chinese participants. The safety profile of and exposure to aclidinium was consistent with previous studies conducted in Caucasian populations."

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

Investigation of aclidinium bromide degradation by stability-indicating HPLC methods, characterization of impurities by NMR, and identification of degradation products by LC-MS. (PubMed, J Pharm Biomed Anal) - "The stress and photostability testing studies showed that the aclidinium bromide drug substance is not sensitive to elevated temperature (105 °C, 10 days), slightly sensitive to daylight and UV-radiation, and it showed significant degradation under all hydrolysis and oxidizing conditions. The related substances HPLC method reported herein is also capable to monitor the potential genotoxic impurity 3-bromopropoxybenzene (3-BPB), a class 2 impurity according to ICH M7, and ensures that the impurity remains below the threshold of toxicological concern (TTC) limit, making it safe for patients."

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

The effect of lung emptying on the airway deposition of aerosol drugs (ERS 2023) - "Table 1. Relative change of the lung dose as a result of forceful breathe-out in comparison to no breathe-out Drug name Average relative change of lung dose (%) Significance of lung dose change at p=0.05 Onbrez Breezhaler -6.7 significant decrease Relvar Ellipta -1.4 insignificant decrease Seebri Breezhaler -1.1 insignificant decrease Bretaris Genuair 0.3 insignificant increase Foster NEXThaler 3.0 significant increase Bufomix Easyhaler 5.5 significant increase Symbicort Turbuhaler 9.6 significant increase; Respiratory intensive care; Epidemiology; Pulmonary function testing; Cell and molecular biology; General respiratory patient care; Public health"

Critical care

SPC Korea, exclusive domestic distribution of two COPD new drugs [Google translation] (Daily Pharm) - "SPC Korea will be in charge of domestic supply of two COPD new drugs....Since the 1st, the company has been contracting with COVIS Pharma GmbH...to treat chronic obstructive pulmonary disease (COPD), 'Eclira (aclidinium bromide)' and 'Duarclear (aclidinium)'. bromide, formoterol)' for domestic exclusive sales and distribution....A company official said, 'With this contract, we will strengthen the company's existing respiratory treatment portfolio and provide new treatment options in Korea through the introduction of excellent global new drugs.'"

Commercial • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

PASS: Aclidinium Bromide Post-Authorisation Safety Study to Evaluate the Risk of Cardiovascular Endpoints (clinicaltrials.gov) - P=N/A | N=26839 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jun 2022 | Trial primary completion date: Dec 2022 ➔ Jun 2022

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

Covis Pharma Announces Positive Topline Results from the AVANT Phase 3 Clinical Trial Showing Significant Improvement in Patients with Moderate to Severe Stable COPD (GlobeNewswire) - P3 | N=1,067 | AVANT (NCT03022097) | Sponsor: AstraZeneca | "Covis Pharma Group ('Covis')...announced positive topline results from the AVANT phase 3 clinical trial for Duaklir® (aclidinium bromide 400µg /formoterol 12µg twice-daily) and Eklira® (aclidinium bromide 400µg twice-daily) – known as Tudorza® in the U.S. This 24-week study achieved statistically significant and clinically important outcomes for all key endpoint measures of efficacy in adult patients with moderate to severe stable chronic obstructive pulmonary disease (COPD)....Detailed results of the study are planned for future publication....A full analysis of the AVANT data is ongoing with complete results to be provided, or submitted with the AVANT NDA, to the China Food and Drug Administration (CFDA)."

P3 data: top line • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Effect of Peak Inspiratory Flow Data on Physician Prescribing Practices of Dry Powder Inhalers for COPD Patients (ATS 2022) - "Suboptimal PIF was defined as <60 L/min for patient’s using DPI with medium-low resistance (Diskus and Ellipta), <45 L/min for medium resistance (Pressair), < 30 L/min for high resistance (Handihaler)...Despite calls for physicians to consider PIF in their choice of inhaler for COPD patients, in our study that rarely occurred in clinical practice despite providing PIF data to prescribers. Further study is needed to determine the clinical implications of suboptimal PIF on patient outcomes, physician knowledge and practice patterns in relationship to PIF data and prescription decision-making."

Clinical • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

AVANT: Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients (clinicaltrials.gov) - P3 | N=1067 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

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

Covis Completes Acquisition of Global Respiratory Portfolio of Two Medicines from AstraZeneca (GlobeNewswire) - "Covis Pharma Group...announced today that Covis Pharma GmbH has completed the acquisition of Eklira® (aclidinium bromide), known as Tudorza® in the US and marketed as Bretaris® in some countries, and Duaklir® (aclidinium bromide/formoterol), marketed as Brimica® in some countries, from AstraZeneca (the 'Acquisition'). Under the terms of the Acquisition agreement, AstraZeneca received a payment of $270m from Covis. AstraZeneca will also receive payments in respect of certain ongoing development costs related to the medicines."

Licensing / partnership • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

AVANT: Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients (clinicaltrials.gov) - P3; N=1066; Active, not recruiting; Sponsor: AstraZeneca; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants (clinicaltrials.gov) - P1; N=20; Completed; Sponsor: AstraZeneca; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants (clinicaltrials.gov) - P1; N=20; Active, not recruiting; Sponsor: AstraZeneca; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: AstraZeneca; Not yet recruiting ➔ Recruiting; Trial completion date: Sep 2021 ➔ Dec 2021; Trial primary completion date: Sep 2021 ➔ Dec 2021

Clinical • Enrollment open • Trial completion date • Trial primary completion date

Covis Significantly Strengthens Global Respiratory Portfolio Through Acquisition of Two Medicines from AstraZeneca (GlobeNewswire) - "Covis Pharma Group...announced today that Covis Pharma GmbH has acquired Eklira® (aclidinium bromide), known as Tudorza® in the US and marketed as Bretaris® in some countries, and Duaklir® (aclidinium bromide/formoterol), marketed as Brimica® in some countries, from AstraZeneca....Covis will pay AstraZeneca US$270m on completion. Covis will also cover certain ongoing development costs related to the medicines....The transaction is expected to complete in the fourth quarter of 2021, subject to customary closing conditions and regulatory clearances."

Licensing / partnership • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Efficacy of Aclidinium Bromide According to Baseline Therapy: Post-Hoc Analysis of ASCENT-COPD Randomized Trial. (PubMed, Adv Ther) - P4 | "In patients with moderate-to-severe COPD and CV risk factors, the addition of aclidinium to maintenance therapy with LABA or LABA + ICS provided further benefit."

Clinical • Journal • Retrospective data • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

AVANT: Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients (clinicaltrials.gov) - P3; N=1060; Recruiting; Sponsor: AstraZeneca; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

AVANT: Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients (clinicaltrials.gov) - P3; N=1060; Active, not recruiting; Sponsor: AstraZeneca; Trial completion date: Jul 2021 ➔ May 2022; Trial primary completion date: Jul 2021 ➔ May 2022

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

Current position of new fixed-dose combination of tiotropium and olodaterol - its role in the treatment of chronic obstructive pulmonary disease in the Czech Republic (PubMed) - "...All other drugs (inhaled-corticosteroids, mucoactive medication, roflumilast, antibiotics), and non-pharmacological (lung volume reductions, nutrition support, long-term oxygen, home non-invasive ventilation, lung transplantation, palliative care) procedures are intended for a specific subgroups of patients only...Currently we can use four original drug combinations: titropium + olodaterol, glycopyrronium + indacaterol, umeklidinium + vilanterol and aclidinium + formoterol in the Czech Republic...Unfortunately "face to face" comparison of different drug combinations is still missing. However, the treatment with tiotropium + olodaterol combination has been demonstrated to significantly (35 %) reduce the occurrence of clinically significant deterioration, which may lead to the stabilization of this multicomponent disease.Key words: COPD - hospitalizations - inhaled bronchodilators - mortality - treatment."

Journal • Biosimilar • Chronic Obstructive Pulmonary Disease • Immunology

Role of budesonide, formoterol fumarate and aclidinium bromide in the inflammaging of airway epithelial cells (ERS 2017) - "A combination of BUD, ACL and FO is able to counteract the effects of CSE on the LPS binding, FoxO3 nuclear expression, ERK 1/2 pathway activation, survivin and IL-8 mRNA expression. Conclusions.These findings suggest a new effect of combination with BUD, ACL and FO in counteracting inflammaging processes induced by cigarette smoke exposure."

Preclinical • Biosimilar • Chronic Obstructive Pulmonary Disease • Immunology