Aralast NP (alpha 1-antitrypsin) / Omni Bio Pharma, Takeda - LARVOL DELTA

Application of an Artificial Intelligence Model to Detect Alpha-1 Antitrypsin Deficiency: Model Performance (ATS 2025) - "A previously developed machine learning model for identifying patients with AATD was successfully calibrated and validated using patient data from the Cleveland Clinic EMR. As measured by ROC and PR on unseen validation data, the model achieved high levels of performance, demonstrating differentiation between AATD and similar conditions or randomly selected controls."

Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Application of an Artificial Intelligence Model to Detect Alpha-1 Antitrypsin Deficiency: Characterizing the Study Population (ATS 2025) - "Within the Cleveland Clinic EMR, this analysis identified phenotypic and treatment pattern differences among cohorts of patients confirmed to have AATD. Lower frequencies of comorbidities, as well as lower rates of patients who received augmentation therapy for AATD, were observed in patients with mild deficiency of AAT compared with patients with confirmed genetic diagnoses and those with severe deficiency of AAT."

Clinical • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases

Clinical Study Support by Long-Term Stability Studies of Alpha1-Proteinase Inhibitor and Urea in Relevant Biological Matrices. (PubMed, Pharmaceuticals (Basel)) - "Interestingly, the analyte concentration did not significantly influence the results in either of the sample matrices. The data confirmed the appropriate stability of the three analytes in the matrices of citrated plasma and BAL-mimicking samples for at least up to 15 months."

Journal • ELANE

Liver disease progression in patients with alpha-1 antitrypsin deficiency and a Pi*ZZ genotype: a retrospective natural history study (EASL 2025) - "Among pts with AATD and a Pi*ZZ genotype, almost one in four experienced liver disease progression by 3.5 years based on matched fibrosis staging methods. Pts with more advanced fibrosis may have a higher proportion of liver disease progression. Study/writing funding: Takeda Development Center Americas, Inc."

Retrospective data • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Pulmonary Disease • Respiratory Diseases

Estimating the diagnosis rate of alpha-1 antitrypsin deficiency: insights from population-based cohorts in the USA (EASL 2025) - "In this study, < 2.0% of individuals with AATD genotypes had an AATD Dx code in their EMR. Those with a Dx had a higher prevalence of liver/lung disease and other comorbidities than those without a Dx in their EMR. Among those with a Pi*ZZ genotype, AATD Dx rate ranged from ~50–70%, which may be attributed to greater symptom manifestations associated with this genotype."

Clinical • Alpha-1 Antitrypsin Deficiency • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Obesity • Pulmonary Disease • Respiratory Diseases

Takeda: The alpha-1 antitrypsin deficiency liver care journey: From early signs to effective strategies (EASL 2025) - "Sponsored by Takeda. Recall the tools and strategies available to ensure a timely diagnosis of alpha-1 antitrypsin deficiency (AATD)-associated liver diseaseIdentify early signs of AATD-associated liver disease, including recognizing potential indicators in asymptomatic patients Outline a collaborative care plan for people with AATD-associated liver disease, incorporating pulmonology and hepatology perspectives Describe current and future AATD-associated liver disease management strategies"

Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Longitudinal assessment of liver stiffness for up to 96 weeks by magnetic resonance elastography and correlation with fibrosis markers in alpha-1 antitrypsin deficiency-associated liver disease: results from phase 2 studies of fazirsiran (EASL 2025) - P2 | "LSM via MRE demonstrated promising utility in monitoring fazirsiran treatment response in a small cohort of pts with AATD-LD. The utility of LSM via MRE and FibroScan will be further evaluated in ongoing phase 3 trials. Study/writing funding: Takeda Development Center Americas, Inc."

P2 data • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases

Artificial intelligence-driven qFibrosis® in alpha-1-antitrypsin deficiency-associated liver disease: correlation with METAVIR stage and other disease specific features (EASL 2025) - P2 | "This study aimed to compare second harmonic generation/two-photon excitation (SHG/TPE) and AI-driven qFibrosis analyses to pathologist-reported METAVIR fibrosis stage, non-invasive tests (NITs) of fibrosis and intrahepatic Z-alpha-1 antitrypsin (Z-AAT) burden using data from phase 2 clinical trials of fazirsiran... qFibrosis stage (METAVIR) and continuous value correlated with pathologist-reported METAVIR fibrosis stage, LSM via FibroScan/MRE and APRI, and identified a spatial correlation with distribution of Z-AAT burden. This suggests value in qFibrosis, an AI-driven, fully quantitative measure of fibrosis and its zonal distribution in AATD-LD. Novel digital pathology approaches may support therapeutic development in AATD-LD but require validation in larger cohorts."

Alpha-1 Antitrypsin Deficiency • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases

Fazirsiran for alpha-1 antitrypsin deficiency-associated liver disease: long-term efficacy and safety results from a phase 2 extension study (EASL 2025) - P2 | "Fazirsiran showed sustained activity and long-term (≤ 3 years) safety in pts with AATD- LD during the extension phase. Fazirsiran was associated with reductions in liver/serum Z-AAT, improvements in measures of AATD-LD and a long-term safety profile that supports further clinical development in pts with AATD-LD. Study/writing"

Clinical • P2 data • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Patient-level analysis of intrahepatic z-alpha-1 antitrypsin burden in patients with alpha-1 antitrypsin deficiency-associated liver disease following fazirsiran treatment (EASL 2025) - P2, P3 | "A robust and sustained reduction of intrahepatic Z-AAT burden in patients with AATD-LD following fazirsiran treatment was demonstrated using two independent analytical approaches (PAS-D and LC–MS). Current findings will be validated in an ongoing phase 3 trial (NCT05677971) in which the effect of fazirsiran on the reversal of liver fibrosis in patients with AATD-LD will be evaluated. Study/writing"

Clinical • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases

Patient experience of alpha-1 antitrypsin deficiency-associated liver disease: a qualitative study. (PubMed, Qual Life Res) - "Several concepts were frequently reported as moderately/highly bothersome/disturbing. Further investigation of the experience of patients with AATD-LD in a large, diverse population across all fibrosis stages and genotypes is warranted. Clinical outcome assessments that capture salient concepts are needed."

Journal • Alpha-1 Antitrypsin Deficiency • Back Pain • CNS Disorders • Fatigue • Fibrosis • Gastroesophageal Reflux Disease • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Musculoskeletal Pain • Pain • Pulmonary Disease • Respiratory Diseases • Sleep Disorder

An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease (clinicaltrials.gov) - P3 | N=37 | Active, not recruiting | Sponsor: Takeda | Trial completion date: May 2026 ➔ May 2033 | Trial primary completion date: May 2026 ➔ May 2033

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • AFP

Clinical and Economic Outcomes in Patients With Alpha-1 Antitrypsin Deficiency in a US Medicare Advantage Population. (PubMed, J Health Econ Outcomes Res) - " Further research is needed to assess the impact of improved AATD testing on those with COPD. Increased awareness, earlier testing, and treatment may reduce the healthcare burden of AATD in the US Medicare population."

HEOR • Journal • Medicare • Reimbursement • US reimbursement • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Fibrosis • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Characterization of Alpha-1 Antitrypsin Function in ANCA-Associated Vasculitis (ACR Convergence 2024) - "A1AT genotype among people with AAV is associated with differences in age at diagnosis and clinical diagnosis. A1AT antigen levels and activity reflect A1AT genotypes and act as acute-phase reactants, but are not associated with disease status."

ANCA Vasculitis • Vasculitis • CXCL8 • IL10 • IL13 • IL6 • SERPINA1

An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease (clinicaltrials.gov) - P3 | N=37 | Active, not recruiting | Sponsor: Takeda | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • AFP

Alpha-1 Antitrypsin Deficiency: Are You Overlooking a Leading Genetic Culprit in Liver Disease? (AASLD 2024) - "This interactive symposium features a multispecialty expert panel to provide insights into the pathophysiologic and genetic underpinnings, best practices in diagnosing, and navigating the management of AATD liver disease. For more information and to register, visit: https://clinicaloptions.com/events/alpha-1-antitrypsin-deficiency-liver-disease/12491 Identify clinical manifestations of AATD-LD Position recommended diagnostic procedures for suspected AATD-LD Implement noninvasive tests to assess liver fibrosis in patients with AATD-LD Summarize investigational therapeutic approaches for AATD-LD"

Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases

LONG-TERM SAFETY AND EFFICACY OF FAZIRSIRAN IN PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE ENROLLED IN THE PHASE 2 PLACEBO-CONTROLLED SEQUOIA TRIAL (AASLD 2024) - "Fazirsiran showed sustained activity and long-term safety in patients with AATD-LD during the OLE phase. Fazirsiran was associated with stable pulmonary function, reduced serum Z-AAT, improved laboratory measures and a safety profile that supports its further clinical development in patients with AATD-LD. Writing assistance provided by R Tooze, PhD, of Oxford PharmaGenesis."

Clinical • P2 data • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases

CONCORDANCE OF HISTOLOGICAL AND LIQUID CHROMATOGRAPHY MASS-SPECTROMETRY-BASED INTRAHEPATIC Z-ALPHA-1 ANTITRYPSIN (Z-AAT) BURDEN ASSESSMENTS IN PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE (AASLD 2024) - P2 | "We leveraged data from two clinical trials of fazirsiran, an investigational small interfering RNA therapy for AATD-LD, to assess the correlations between PAS-D, intrahepatic Z-AAT and serum Z-AAT... PAS- D and LC-MS, two valuable approaches for the measurement of intrahepatic Z-AAT in patients with AATD-LD, demonstrated good concordance cross-sectionally and longitudinally, despite differences in pre-analytical procedures, analytical characteristics and inherent biases. These biopsy- and serum-based Z-AAT biomarkers are valuable tools to support clinical development of emerging therapies in AATD-LD. Writing assistance provided by EL Wescott, PhD, of Oxford PharmaGenesis."

Clinical • Discordant • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

THE PLASMA PROTEOMIC PROFILE OF SUBJECTS WITH THE SERPINA1 PI*ZZ GENOTYPE CORRELATES WITH LIVER DISEASE SIGNATURES: AN ANALYSIS OF POPULATION-LEVEL DATA FROM THE UK BIOBANK PROTEOMICS PROJECT (AASLD 2024) - "This study identified a conserved serum proteomics signature between subjects with a Pi*ZZ genotype and patients with chronic liver diseases due to other etiologies. Potential use of these markers in the diagnosis, treatment response, and monitoring of AATD-associated liver disease requires further investigation. Lung function-related proteomics signatures in patients with the Pi*ZZ genotype are being actively examined."

Clinical • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases • SERPINA1

PREVALENCE ESTIMATES OF GENOTYPES ASSOCIATED WITH ALPHA-1 ANTITRYPSIN DEFICIENCY: A RETROSPECTIVE COHORT STUDY IN THE USA (AASLD 2024) - "This population-based approach showed AATD genotype estimates are much higher than expected, and greater than previously reported in the UK Biobank, which comprises a homogenous population of predominantly White individuals. After standardization, we found that up to 76 per 100,000 individuals had the Pi*ZZ genotype, known to have the highest risk for LgD and LD. Estimates varied across data sources, suggesting that prevalence differs based on the population tested, adding complexity to our understanding of AATD prevalence."

Retrospective data • Alpha-1 Antitrypsin Deficiency • Atherosclerosis • Cardiovascular • Dyslipidemia • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • Women's Health • SERPINA1

DISEASE PROGRESSION IN ADULT PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER CIRRHOSIS: A RETROSPECTIVE COHORT STUDY OF THE US VETERANS AFFAIRS HEALTH DATABASE (AASLD 2024) - "Disease progression to HD or HCC was similar among patients with cirrhotic AATD-LD across Pi*Z variants. Patients with cirrhosis and Pi*Z alleles should be closely monitored, particularly those with steatosis, who may derive significant clinical benefit from timely diagnosis. Writing assistance was provided by A Pecchia-Bekkum at Oxford PharmaGenesis, Oxford, UK."

Retrospective data • Alpha-1 Antitrypsin Deficiency • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • SERPINA1

DIGITAL IMAGE QUANTIFICATION OF COLLAGEN PROPORTIONATE AREA CORRELATES WITH METAVIR FIBROSIS STAGE AND LIVER STIFFNESS MEASUREMENT VIA FIBROSCAN® IN ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE (AASLD 2024) - P2 | "We aimed to establish a digital quantification method for collagen proportionate area (CPA) in AATD-LD and compare it with meta-analysis of histological data in viral hepatitis (METAVIR) fibrosis stage and FibroScan® scores using data from phase 2 clinical trials of fazirsiran... CPA significantly correlated with METAVIR fibrosis stage and liver stiffness measurement, suggesting value in continuous scores for quantifying liver fibrosis and potential for its utility as a measure of fibrosis in AATD-LD biopsy to complement pathologist-led histology evaluation. Novel digital pathology approaches may support therapeutic development in AATD-LD but require further validation. Writing assistance provided by R Tooze, PhD, of Oxford PharmaGenesis."

Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases

A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems (clinicaltrials.gov) - P=N/A | N=1000 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases

Machine-Learning Model Identifies Patients With Alpha-1 Antitrypsin Deficiency Using Claims Records. (PubMed, COPD) - "Moreover, patients with diagnosed AATD and COPD without AATD had unique cadences of similar medical events in their diagnostic journeys. Our work shows that a machine-learning model trained on a large US claims database can accurately identify symptomatic patients with AATD and provides useful insights into the diagnostic journey of patients with AATD."

Journal • Machine learning • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Retrospective Database Analysis of Liver-Related Clinical Events in Adult and Pediatric Patients with Alpha-1 Antitrypsin Deficiency in the United States. (PubMed, Hepat Med) - "No liver transplantations occurred in patients aged 6-17 years. Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events."

Journal • Retrospective data • Alpha-1 Antitrypsin Deficiency • CNS Disorders • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hepatic Encephalopathy • Hepatocellular Cancer • Hepatology • Oncology • Pediatrics • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Transplantation