Cayston (aztreonam lysine) / Gilead - LARVOL DELTA

Medicines optimisation: Using adherence to support supply (ECFS 2024) - "The most cost savings were generated from Cayston nebuliser, this could be because it is one of the more expensive nebuliser treatments equating to £2,181.53 for a month's supply... The enhanced role of the pharmacy technician reduces the burden of work from the multidisciplinary team. Pharmacy technicians are ideally placed to carry out homecare prescription reviews and cost saving exercises. As this project has shown, many substantial cost savings and optimisation come with nebuliser treatments."

Adherence

Colonisation of a 4-month-old cystic fibrosis child by Burkholderia cenocepacia : treatment adaptation after relapse and strains genomic comparison (ECFS 2024) - "Following a close collaboration between CF physicians and bacteriologists, a new IV course was decided with ceftazidime and levofloxacine, followed by a 3 months inhaled course of alternating nebulised tobramycin and aztreonam Lysine indicated in CF. Bc is associated with high morbidity in people with CF. Despite the lack of treatment guideline, cotrimoxazole, ceftazidime and meropenem are considered as useful molecules. Regardless of natural resistances to aztreonam and tobramycine, these molecules were used in relay of IV antibiotics and no relapse was observed since September 2023 until now."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Proteomics unveils unique host and microbial signatures linked to key clinical trial outcomes in cystic fibrosis trials (ECFS 2024) - " This post-hoc analysis of the Aztreonam Lysine for Treatment of Exacerbations of CF (AZTEC-CF) study assessed host-associated biomarker levels and proteomic changes in response to antibiotic treatment and explored how these were linked to clinical trial outcomes... These results suggest changes in two key CF clinical trial outcomes (FEV1 and CFQ-R) are not well correlated with microbiological changes and instead may be underpinned by different host physiological mechanisms. Understanding these divergent mechanisms is vital to underpin optimal clinical trial design in CF in the modulator era."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

TWO CASES OF SUCCESSFUL ERADICATION OF BURKHOLDERIA CEPACIA IN PEDIATRIC PATIENTS WITH CYSTIC FIBROSIS (ESPID 2024) - "Two months later, she received a 2-week course of intravenous meropenem, oral cotrimoxazole, and inhaled aztreonam lysine. Based on our experience, we recommend initiating eradication procedures as soon as Bc is identified in cultures. Further case reports and clinical studies may provide additional support for our preliminary findings."

Clinical • Cognitive Disorders • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases • Transplantation

Inhaled aztreonam lysine in the management of Pseudomonas aeruginosa in patients with cystic fibrosis: real-life effectiveness. (PubMed, Eur J Hosp Pharm) - "AZLI achieved stabilisation of lung function measured by FEV in patients with CF and chronic P. aeruginosa infection, along with an adequate safety profile."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases

PROTEOMICS REVEALS DISTINCT DRIVERS OF CYSTIC FIBROSIS LUNG FUNCTION AND QUALITY OF LIFE OUTCOMES: POST-HOC ANALYSIS OF THE AZTEC-CF STUDY (BTS WM 2023) - "In this post-hoc analysis of the Aztreonam Lysine for Treatment of Exacerbations of CF (AZTEC-CF) study we investigated proteomic changes in response to treatment and how these changes related to the clinical trial outcomes...Conclusion These results suggest changes in two key CF clinical trial outcomes (lung function and quality of life) may be underpinned by different pathophysiological mechanisms. Understanding these divergent mechanisms is vital to underpin optimal clinical trial design in CF in the modulator era."

HEOR • Retrospective data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A CASE REPORT ON THE USE OF TRIKAFTA ON A PREGNANT PATIENT WITH CYSTIC FIBROSIS (CHEST 2023) - "Her medications were shifted to consider the pregnancy and was started on azithromycin, Cayston, and weaned off sertraline...In March 2023, patient was admitted for 11 days for CF exacerbation and tested positive for COVID and human metapneumovirus while continuing on her home medications and treated with meropenem, colistin, and linezolid with pyridoxine... Our case highlights the importance of utilizing an individualized approach to benefit maternal health during pregnancy. There should be an informed discussion to the patient on the risks and benefits of Trikafta and CF management prior to pregnancy. Although research still needs to be conducted on the safety of Trikafta and its long-term effects, there is value in its role in increasing fertility in women with CF."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infertility • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CFTR

ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis. (PubMed, J Cyst Fibros) - P3b | "Non-inferiority of 14-day AZLI versus 28-day AZLI was not demonstrated. Both courses were well tolerated, further supporting AZLI short-term safety in paediatric and adolescent pwCF."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. (PubMed, Cochrane Database Syst Rev) - "We found that nebulised antibiotics, alone or with oral antibiotics, were better than no treatment for early infection with P aeruginosa. Eradication may be sustained in the short term. There is insufficient evidence to determine whether these antibiotic strategies decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials comparing two active treatments have failed to show differences in rates of eradication of P aeruginosa. One large trial showed that intravenous ceftazidime with tobramycin is not superior to oral ciprofloxacin when inhaled antibiotics are also used. There is still insufficient evidence to state which antibiotic strategy should be used for the eradication of early P aeruginosa infection in CF, but there is now evidence that intravenous therapy is not superior to oral antibiotics."

Journal • Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

The impact of the COVID-19 pandemic and elexacaftor/tezacaftor/ivacaftor initiation on high-cost medication utilisation in adults living with cystic fibrosis (ECFS 2023) - "In this study, we aimed to assess the impact of these events on other high-cost medication utilisation. We interrogated the requests for delivery of tobramycin nebuliser solution (TNS), inhaled aztreonam lysine (AZLI), dornase alfa, colomycin and ETI via the homecare service at our large regional adult CF centre. During the COVID-19 pandemic lockdown in the UK, only dornase alfa utilisation increased. However, post lockdown our pwCF are using other high-cost medications less frequently. This may reflect their wish to reduce the CF treatment burden following the introduction of ETI and the improved health this confers."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

In vitro efficacy of inhalative antibiotics against Pseudomonas aeruginosa using artificial sputum medium (ECFS 2023) - "Most commonly, inhalative antibiotics (tobramycin, colistin, aztreonam lysine, levofloxacin), that generate high local concentrations with low systemic drug concentrations and low systemic side effects, are used. Using artificial sputum medium levofloxacin was the most active antipseudomonal agent with a high killing activity for all P. aeruginosa isolates tested."

Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases

VitalBE: Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: University of Dundee | Active, not recruiting ➔ Recruiting | Trial completion date: Jun 2022 ➔ Sep 2025 | Trial primary completion date: Jun 2022 ➔ Sep 2025

Enrollment open • Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Public Advisory - Two lots of cystic fibrosis drug Cayston recalled due to the potential of cracked glass vials (Canada Newswire) - "Health Canada is advising the public that Gilead Sciences Incorporated recalled two lots (032168 and 033357) of the cystic fibrosis drug Cayston (aztreonam) (DIN 02329840) on March 1, 2023, due to the potential of cracked glass vials in those lots, which may introduce glass particles into the medication."

Clinical • Cystic Fibrosis • Respiratory Diseases

Role of Inhalational Aztreonam Lysine in Lower Airway Infections in Cystic Fibrosis: An Updated Literature Review. (PubMed, Cureus) - "Hence, inhalational therapy with AZLI is highly efficacious and safe in the management of chronic airway infections. More clinical trials need to be conducted in the future to assess its long-term clinical benefits and adverse events as well as to explore the role of AZLI in the setting of acute lung infections."

Journal • Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis. (PubMed, Cochrane Database Syst Rev) - "Long-term treatment with inhaled anti-pseudomonal antibiotics probably improves lung function and reduces exacerbation rates, but pooled estimates of the level of benefit were very limited. The best evidence available is for inhaled tobramycin. More evidence from trials measuring similar outcomes in the same way is needed to determine a better measure of benefit. Longer-term trials are needed to look at the effect of inhaled antibiotics on quality of life, survival and nutritional outcomes."

Journal • Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases

Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease (clinicaltrials.gov) - P2; N=5; Terminated; Sponsor: Virginia Commonwealth University; N=10 ➔ 5; Completed ➔ Terminated; terminated due to an inability to recruit study subjects

Enrollment change • Trial termination • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Otorhinolaryngology • Respiratory Diseases

ALPINE2: efficacy and safety of 14-day vs 28-day aztreonam for inhalation solution for Pseudomonas aeruginosa eradication in children and adolescents with cystic fibrosis (ECFS 2022) - No abstract available

Clinical • Late-breaking abstract • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

ALPINE2: Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria (clinicaltrials.gov) - P3b | N=149 | Terminated | Sponsor: Gilead Sciences | Completed ➔ Terminated; Study was terminated early by sponsor due to the challenges and risks introduced by Coronavirus disease 2019 (COVID-19) pandemic.

Trial termination • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases

Blood mRNA biomarkers distinguish variable systemic and sputum inflammation at treatment initiation of inhaled antibiotics in cystic fibrosis: A prospective non-randomized trial. (PubMed, PLoS One) - P=N/A | "In the current study, we tested whether the same panel predicted clinical response in subjects receiving a month of inhaled antibiotic therapy with aztreonam lysine (AZLI; Cayston®)...Given the size limitation of the study, larger studies are needed in order to evaluate whether molecular measures may add precision to the determination of infectious and inflammatory outcomes following courses of inhaled antimicrobial therapies. Clinical Trials.gov Identifier: NCT01736839."

Biomarker • Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CRP

Observational Study in Cystic Fibrosis Patients Using TOBI® PODHALER® or Other FDA Approved Inhaled Antipseudomonal Antibacterial Drugs (clinicaltrials.gov) - P=N/A | N=409 | Completed | Sponsor: Mylan Inc. | Active, not recruiting ➔ Completed | N=260 ➔ 409 | Trial completion date: Jul 2023 ➔ Dec 2021 | Trial primary completion date: Jul 2023 ➔ Dec 2021

Enrollment change • FDA event • Trial completion • Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

ALPINE2: Safety and Efficacy of 2 Treatment Regimens of Aztreonam for Inhalation Solution in Children With Cystic Fibrosis and New Onset Pseudomonas Aeruginosa Infection (clinicaltrials.gov) - P3b; N=149; Completed; Sponsor: Gilead Sciences; Active, not recruiting ➔ Completed

Clinical • Trial completion • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases

VitalBE: Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis (clinicaltrials.gov) - P2; N=100; Active, not recruiting; Sponsor: University of Dundee; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

VitalBE: Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: University of Dundee; Trial completion date: Jun 2021 ➔ Jun 2022; Trial primary completion date: Jun 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

VitalBE: Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: University of Dundee; Trial completion date: Oct 2020 ➔ Jun 2021; Trial primary completion date: Oct 2020 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Aztreonam Lysine Increases the Activity of Phages E79 and phiKZ against Pseudomonas aeruginosa PA01. (PubMed, Microorganisms) - "A one-step growth curve indicates that phiKZ in the presence of AzLys also exhibits a decreased infection latency and moderately undergoes accelerated time to lysis. In contrast to prior PAS studies demonstrating that phages undergo delayed time to lysis with cell filamentation, these PAS results show that phages undergo accelerated time to lysis, which therefore suggests that PAS is dependent upon multiple factors, including the type of phages and antibiotics used, and the bacterial host being tested."

Journal