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

Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain. (PubMed, Biomolecules) - "Veratridine-evoked Ca2+ responses, a sodium-channel-dependent readout of nociceptor activity, were suppressed by hAAT to a degree comparable to the selective sodium channel inhibitors ProTx-II (NaV1.7) and VX-548 (NaV1.8), driven by loss of the nociceptor-associated response profiles. In vivo, hAAT decreased pain sensitivity and pain-associated behaviors in both inflammatory and neuropathic models. Together, these findings reveal a mechanism by which hAAT suppresses nociceptor activity and position Aralast NP® as a safe, effective candidate for treating chronic pain."

Journal • Addiction (Opioid and Alcohol) • Inflammation • Neuralgia • Pain • NAV1 • SERPINA6

Beyond cirrhosis: Major adverse liver outcomes across homozygous and heterozygous Alpha-1 antitrypsin deficiency associated liver disease. (PubMed, Hepatology) - "In this national longitudinal cohort of veterans with documented AATD genotype testing and median follow-up of 15.9 years, we observed an increased risk of MALO in both homozygous and heterozygous Z-allele carriers, underscoring the need for timely diagnosis and enhanced clinical surveillance among veterans with known AATD genotypes."

Adverse events • Journal • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Transplantation

A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems (clinicaltrials.gov) - P=N/A | N=500 | Recruiting | Sponsor: Takeda | Trial completion date: Apr 2032 ➔ Dec 2031 | Trial primary completion date: Apr 2032 ➔ Dec 2031

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

Characterization of US patients with alpha-1 antitrypsin deficiency treated with an alpha-1 proteinase inhibitor. (PubMed, J Med Econ) - "Currently, specific therapy for alpha-1 antitrypsin deficiency (AATD) consists solely of augmentation therapy with alpha-1 proteinase inhibitors, including Glassia (Alpha1-PI)...As a result, proportion of days covered and observed treatment patterns may be overestimated and may reflect reimbursement patterns rather than actual use. Patients with AATD had a high burden of comorbidities, treatment discontinuations and switching, and HCRU, demonstrating an unmet need when utilizing Alpha1-PI for augmentation therapy."

Journal • Retrospective data • Alpha-1 Antitrypsin Deficiency • Cardiovascular • Genetic Disorders • Hypertension • Pulmonary Disease • Respiratory Diseases

Liver transplant outcomes and clinical burden in patients with alpha-1 antitrypsin deficiency-associated liver disease in Canada (EASL 2026) - "This is the first natural history study of pts with AATD-LD assessed for OLT. In this study, few pts had available genotype data before OLT (34/341 pts [10%]) and median time from first liver-related clinical event to index date was short (2 months). These data highlight the need for improved disease awareness to diagnose AATD-LD early in the disease trajectory and prevent progression to end-stage liver disease in pts with AATD-LD."

Clinical • Alpha-1 Antitrypsin Deficiency • CNS Disorders • Genetic Disorders • Hepatic Encephalopathy • Hepatology • Pulmonary Disease • Respiratory Diseases • Transplantation

Baseline fibrosis stage predicts risk of progression in patients with alpha-1 antitrypsin deficiency and a protease inhibitor (Pi)*ZZ/SZ genotype: longitudinal data from the Birmingham AATD registry (EASL 2026) - "In pts with AATD and a Pi*ZZ genotype, baseline F2 was associated with higher rates of fibrosis progression versus F0/F1. These findings position F2 fibrosis as a clinically meaningful threshold for intensified hepatic surveillance and risk stratification and may inform the design of future interventional therapies targeting fibrosis progression in AATD-associated liver disease. Study/writing funding: Takeda Development Center Americas, Inc."

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

Natural history of liver disease in patients with alpha-1 antitrypsin deficiency and a protease inhibitor (Pi)*ZZ genotype: data from the Alpha-1 liver network in Germany (EASL 2026) - "Among pts with Pi*ZZ AATD, 11%–71% experienced fibrosis progression during follow-up. Pts with advanced fibrosis may experience higher rates of LD progression. Study/writing funding: Takeda Development Center Americas, Inc."

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

Novel serum proteomic signatures associated with disease burden in alpha-1 antitrypsin deficiency-associated liver disease (EASL 2026) - P2 | " Baseline serum samples from 41 adults with fibrosis and a Pi*ZZ genotype from phase 2 trials (AROAAT- 2001/-2002 [NCT03945292/NCT03946449]) of fazirsiran (an investigational siRNA therapy) were used for biomarker discovery via Olink Explore HT (~5,400 unique proteins)... This study identified novel serum proteins correlated with AATD-LD disease burden, advancing understanding of AATD-LD pathophysiology. Possible use of these markers for diagnosis, prognosis and/or monitoring treatment response in AATD-LD will be investigated in future studies. Study/writing funding: Takeda Development Center Americas, Inc."

Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Pulmonary Disease • Respiratory Diseases • FABP1 • FGFR2 • FSTL1

Fazirsiran treatment reduces serum biomarkers that predict major adverse liver outcomes in patients with alpha-1 antitrypsin deficiency-associated liver disease (EASL 2026) - P2 | "Fazirsiran treatment in pts with AATD-LD reduced levels of circulating biomarkers that predicted MALOs from the UKB-PPP data, supporting evaluation of the therapeutic potential of fazirsiran in a phase 3 clinical trial. Cell-type enrichment and pathway analyses are ongoing to better understand the biological and clinical relevance of these proteins following fazirsiran treatment. Study/writing funding: Takeda Development Center Americas, Inc."

Adverse events • Biomarker • Clinical • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases • GDF15 • IGFBP7 • KRT18 • KRT18 • THBS2

Pulmonary Function Decline in Alpha-1 Antitrypsin Deficiency: A Systematic Review and Meta-Analysis. (PubMed, Int J Chron Obstruct Pulmon Dis) - "This comprehensive SLR and meta-analysis provides an estimate for annual pulmonary function decline in patients with AATD-associated lung disease and highlights an evidence gap in patients with AATD-associated liver disease with or without comorbid lung disease. Further insights into risk factors or potential biomarkers of pulmonary function decline may support clinical strategies for optimizing treatment."

Clinical • Journal • Retrospective data • Review • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • 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=500 | Recruiting | Sponsor: Takeda | N=1000 ➔ 500

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

LIVER DISEASE PROGRESSION IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS WITH AND WITHOUT ALPHA-1 ANTITRYPSIN DEFICIENCY: RESULTS: FROM A RETROSPECTIVE COHORT STUDY IN THE USA (AASLD 2025) - "In this matched cohort study, pts with MASH and AATD were more likely to have LD progression than pts with MASH alone, underscoring the incremental clinical burden associated with AATD. Testing for AATD in pts with MASH may guide treatment decisions and inform monitoring of LD progression. Writing support provided by R Tooze, Oxford PharmaGenesis."

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

SERUM MICRORNA SEQUENCING IDENTIFIED FAZIRSIRAN TREATMENT-RESPONSIVE MICRORNAS IN PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE AND A PI*ZZ GENOTYPE (AASLD 2025) - P2 | "Changes in miRNA expression suggest that there is reduced HSC activity in pts with AATD-LD treated with fazirsiran and support the potential clinical benefit of fazirsiran among pts with AATD-LD and a Pi*ZZ genotype. The utility of these miRNAs as potential non-invasive biomarkers for AATD-LD require validation in larger studies. Writing support provided by M Reynolds, Oxford PharmaGenesis."

Clinical • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • COL3A1 • MIR122 • MIR16 • MIR195 • MIR200 • TGFB1

LIVER DISEASE PROGRESSION IN INDIVIDUALS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED GENOTYPES: INSIGHTS FROM A LARGE GENETIC DATABASE LINKED TO ELECTRONIC MEDICAL RECORDS IN THE USA (AASLD 2025) - "This study leveraged genetic data with linked EMRs and provides evidence that patients carrying the Pi*ZZ genotype have the highest risk of liver disease progression, followed by Pi*SZ and other genotypes. Additionally, a higher APRI score at index was a strong predictor of liver disease progression, underscoring its value in identifying patients at higher risk for liver-related outcomes. Writing support provided by S Chambers, Oxford PharmaGenesis."

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

PERFORMANCE OF VIBRATION-CONTROLLED TRANSIENT ELASTOGRAPHY RELATIVE TO BIOPSY FOR LIVER FIBROSIS STAGING IN PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE AND A PI*ZZ GENOTYPE (AASLD 2025) - "In this study on the performance of VCTE versus liver biopsy for fibrosis staging in adults with AATD-LD and a Pi*ZZ genotype, VCTE performed similarly to biopsy in staging F2/F3 fibrosis. The optimal cut-off values of VCTE-based staging for UoF data were slightly lower than predefined thresholds based on clinical practice. Findings should be interpreted with caution and validated in larger studies."

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

A CLINICAL DECISION SUPPORT TOOL FOR THE IDENTIFICATION OF PATIENTS AT RISK OF DEVELOPING ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE: INTERIM RESULTS: (AASLD 2025) - "The ensemble model provided the best performance of the models evaluated, achieving a 233×- and > 9,300×-fold improvement in AATD-LD diagnosis versus incidence in pts with LD or the general population, respectively, in the SSM/SLU database. Prospective validation is in progress to support use of this AI/ML-CDST for the diagnosis of AATD-LD. Writing support provided by E L Wescott, Oxford PharmaGenesis."

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

LIVER TRANSCRIPTOMIC SIGNATURES IN PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE WITH A PI*ZZ GENOTYPE ARE SIMILAR TO THOSE IN OTHER FIBROTIC LIVER DISEASES (AASLD 2025) - "This is the first known liver transcriptomics study including the Pi*ZZ genotype. In pts with AATD-LD and fibrosis with a Pi*ZZ genotype, transcriptomic profiles were similar to those identified in MASH and PSC. Findings from this study advance the understanding of AATD-LD pathophysiology and highlight potential non-invasive biomarkers with utility in the diagnosis and management of AATD-LD."

Clinical • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Pulmonary Disease • Respiratory Diseases • IL1B • TGFB1

LIVER STIFFNESS RESPONSE AND HETEROGENEITY ASSESSED VIA MAGNETIC RESONANCE ELASTOGRAPHY IN ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE: RESULTS: FROM PHASE 2 STUDIES OF FAZIRSIRAN (AASLD 2025) - P2 | "MRE imaging in AATD-LD using histogram-based spatial LSM distribution and heterogeneity metrics offer additional granularity relative to biopsy. After fazirsiran treatment, heterogeneity metrics indicated a trend towards improved liver stiffness uniformity across fibrotic regions. Further MRE image analyses using radiomics from larger cohorts of pts with AATD-LD may yield robust features for monitoring and predicting treatment response."

Heterogeneity • P2 data • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pulmonary Disease • Respiratory Diseases

Connecting the Clues: Lung and Liver Considerations in Diagnosing Alpha-1 Antitrypsin Deficiency (AASLD 2025) - "Consequences of a delayed AATD diagnosis. Emerging treatment approaches for AATD-associated liver disease Have greater competence related to identifying patients at risk of AATD-associated liver disease Demonstrate greater confidence in their ability to addressing barriers related to the delayed diagnosis of AATD-associated liver disease"

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

FAZIRSIRAN IS EFFECTIVE IN EARLY AND ADVANCED FIBROSIS IN PATIENTS WITH ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE (AASLD 2025) - P2 | "Hepatocellular ASGR1 and SERPINA1 expression is constant in patients with advanced fibrosis stages although loss of parenchymal cells (hepatocytes) may lead to reduced overall ASGR1 expression. Analysis of fazirsiran phase 2 studies indicates that fazirsiran is effective in both advanced and early fibrosis. Collectively, these findings support further development of fazirsiran in patients with AATD-LD and advanced fibrosis, given that accumulation of the disease-causing Z-AAT protein remains high."

Clinical • Metastases • Alpha-1 Antitrypsin Deficiency • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pulmonary Disease • Respiratory Diseases • ASGR • MUC4 • SERPINA1

ARTIFICIAL INTELLIGENCE-BASED QFIBROSIS® ANALYSIS CORRELATES WITH CHANGES IN HISTOLOGICAL FEATURES IN ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE FOLLOWING TREATMENT WITH FAZIRSIRAN (AASLD 2025) - P2 | "METAVIR fibrosis assessed by digital pathology (qF analyses) positively correlated with PAS+D globule burden, portal inflammation, interface hepatitis and hepatocyte cell death in liver biopsy samples from patients with AATD-LD. This study suggests a spatial and pathobiological relationship between change in disease-driving Z-AAT globule burden and changes in portal inflammation and liver fibrosis after fazirsiran treatment. AI-based digital pathology approaches may support therapeutic development in AATD-LD but require validation in larger cohorts with longer observation periods."

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

Bioanalytical Method Validations of Three Alpha1-Antitrypsin Measurement Methods Required for Clinical Sample Analysis. (PubMed, Pharmaceuticals (Basel)) - "Furthermore, the short-time stability of the analyte was also demonstrated. All three AAT measurement methods met the acceptance criteria defined by the guidelines on bioanalytical assay validation, qualifying these methods for clinical sample analysis."

Journal • Alpha-1 Antitrypsin Deficiency • ELANE

Anti-inflammatory Therapy to Improve Outcomes After TPIAT (clinicaltrials.gov) - P4 | N=43 | Completed | Sponsor: University of Minnesota | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Pancreatitis • Transplantation

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