Zemaira (human alpha-1 antitrypsin intravenous) / CSL Behring - LARVOL DELTA

Phase 4, Double-blind Study Evaluating the Response on Computed Tomography (CT) Lung Density Decline Rates of Respreeza / Zemaira Weekly for 3 Years in Adults With alpha1 Antitrypsin Deficiency (AATD) (clinicaltrials.gov) - P4 | N=270 | Not yet recruiting | Sponsor: CSL Behring | Initiation date: Jan 2026 ➔ Apr 2026

Trial initiation date • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Pulmonary Disease • Respiratory Diseases

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Recruiting | Sponsor: CSL Behring | Trial completion date: Sep 2024 ➔ Mar 2027 | Trial primary completion date: Mar 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Not yet recruiting | Sponsor: CSL Behring

New P2/3 trial • Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Recruiting | Sponsor: CSL Behring | Trial completion date: Feb 2023 ➔ Mar 2025

Trial completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Recruiting | Sponsor: CSL Behring | Trial completion date: Mar 2025 ➔ Sep 2024 | Trial primary completion date: Sep 2022 ➔ Mar 2024

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Recruiting | Sponsor: CSL Behring | Trial completion date: Sep 2031 ➔ Oct 2029 | Trial primary completion date: Mar 2031 ➔ Apr 2028

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=310 | Recruiting | Sponsor: CSL Behring | Trial completion date: Mar 2027 ➔ Sep 2031 | Trial primary completion date: Sep 2025 ➔ Mar 2031

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

Phase 4, Double-blind Study Evaluating the Response on Computed Tomography (CT) Lung Density Decline Rates of Respreeza / Zemaira Weekly for 3 Years in Adults With alpha1 Antitrypsin Deficiency (AATD) (clinicaltrials.gov) - P4 | N=270 | Not yet recruiting | Sponsor: CSL Behring

New P4 trial • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Pulmonary Disease • Respiratory Diseases

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

MODULAATE: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (clinicaltrials.gov) - P2/3 | N=222 | Active, not recruiting | Sponsor: CSL Behring | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2029 ➔ Mar 2026 | Trial primary completion date: Apr 2028 ➔ Mar 2026

Enrollment closed • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Multiple Myeloma • Myelodysplastic Syndrome • Transplantation

ELEVAATE: Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=99 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

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

Respreeza® Self-administration and Learning Program (AmAREtTI Study) (clinicaltrials.gov) - P=N/A | N=15 | Completed | Sponsor: CSL Behring | Active, not recruiting ➔ Completed | N=60 ➔ 15

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

ELEVAATE: Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Ex vivo study on the relationship between the circadian clock of blood neutrophils and the effects of alpha1-antitrypsin therapy (ERS 2024) - "Blood was incubated alone or with 2 mg/ml AAT (Respreeza) and/or 5 µg/ml lipopolysaccharide (LPS) from Escherichia coli for 30 min...Overall, our data show that short exposure of the blood to exogenous AAT has an impact on the neutrophil phenotype and that this effect is related to the neutrophil circadian clock. The circadian clock of myeloid cells may influence the efficiency of augmentation therapy and needs further analysis."

Preclinical • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CD14 • CXCL8 • CXCR2 • CXCR4

ELEVAATE: Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Sanofi | Trial completion date: Jun 2025 ➔ Sep 2025

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

Ex vivo study on the human blood neutrophil circadian features and effects of alpha1-antitrypsin and lipopolysaccharide. (PubMed, Vascul Pharmacol) - "The circadian clock of myeloid cells may affect the effectiveness of various therapies, including AAT therapy used to treat patients with AAT deficiency, and needs further investigation."

Journal • Preclinical • Alpha-1 Antitrypsin Deficiency • Respiratory Diseases • CD14 • CDKN1A • CXCL8 • CXCR2

ELEVAATE: Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Inhibrx, Inc. | Trial completion date: Mar 2025 ➔ Jun 2025 | Trial primary completion date: Nov 2024 ➔ May 2025

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

Respreeza® Self-administration and Learning Program (AmAREtTI Study) (clinicaltrials.gov) - P=N/A | N=60 | Active, not recruiting | Sponsor: CSL Behring | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Mar 2025

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

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Trial completion date: Sep 2024 ➔ Mar 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

CSL Behring Demonstrates Continued Commitment to Alpha-1 Community with Addition of ZEMAIRA [Alpha1-Proteinase Inhibitor (Human)] 4- and 5-Gram Vials (PRNewswire) - "SL Behring...announced the availability of 4- and 5-gram vial sizes for ZEMAIRA^® [Alpha1-Proteinase Inhibitor (Human)]. Previously available only in a 1-gram vial, the 4- and 5-gram packaging is significant for the Alpha-1 community as it will streamline the preparation process for ZEMAIRA and reduce waste....ZEMAIRA dosing is weight-based, so a person weighing 183 pounds would require five 1-gram vials. With the 4- and 5-gram vial sizes, healthcare professionals will need to reconstitute fewer ZEMAIRA vials per dose for their patients with Alpha-1. Room temperature storage coupled with the larger vial sizes may also help streamline preparation and administration."

Commercial • Alpha-1 Antitrypsin Deficiency

Purified Versus Plasma Alpha-1 Antitrypsin Effects on Cellular Activities. (PubMed, Methods Mol Biol) - "By adding purified exogenous alpha-1 antitrypsin (AAT) to peripheral blood mononuclear cells in 20% autologous serum and measuring AAT-induced cellular adherence, it was determined that purified AAT differs from plasma AAT. The known association of AAT with lipoproteins and the negative feedback between AAT and low-density lipoprotein (LDL) suggest that purification may separate AAT from a plasma component such as LDL that participates in their normal plasma functions."

Journal • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease

ELEVAATE: Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Inhibrx, Inc.

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

AOTMiT: What will the Transparency Council do in July? [Google translation] (medexpress.pl) - "TRANSPARENCY COUNCIL MEETING No. 27/2023 10 JULY 2023: Respreeza (alpha-1 proteinase inhibitor) CONDITIONAL Indication: within the drug program 'Treatment with human alpha1-proteinase inhibitor in patients with severe alpha1-antitrypsin deficiency and emphysema (ICD10: J44.8 and E88.0)' Decision problem: preparation position on drug evaluation."

Reimbursement • Alpha-1 Antitrypsin Deficiency • Genetic Disorders