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

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

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

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Not yet recruiting ➔ Recruiting

Enrollment open • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

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

New P2 trial • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Initiation date: Jan 2023 ➔ Apr 2023

Trial initiation date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Initiation date: Oct 2022 ➔ Jan 2023

Trial initiation date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Indirect effect of alpha-1-antitrypsin on endotoxin-induced IL-1β secretion from human PBMCs. (PubMed, Front Pharmacol) - "In line, mass spectrometry analysis revealed that AAT (Zemaira) protein contains freer Cys232 than AAT (Prolastin). Our data show that a free Cys232 in AAT is required for controlling LPS-induced IL-1β release from human PBMCs. Further studies characterizing AAT preparations used to treat patients with inherited AAT deficiency remains of clinical importance."

Journal • Alpha-1 Antitrypsin Deficiency • Inflammation • IL1B • SERPINA1

ZEEPS: Zemaira Eosinophilic Esophagitis Pilot Study (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati

New P2 trial • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Respreeza® Self-administration and Learning Program (AmAREtTI Study) (clinicaltrials.gov) - P=N/A | N=60 | Recruiting | Sponsor: CSL Behring | Trial completion date: Mar 2023 ➔ Dec 2023 | Trial primary completion date: Mar 2023 ➔ Dec 2023

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

Therapy to Elevate CD4 Counts in HIV-1 Disease (clinicaltrials.gov) - P2/3; N=4; Completed; Sponsor: Institute for Human Genetics and Biochemistry; Phase classification: P=N/A ➔ P2/3

Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4

Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin. (PubMed, Int J Mol Sci) - "Notably, under the same experimental conditions, the plasma-derived AAT preparation Respreeza (used in native and oxidized forms) did not show significant effects. Our findings imply that an early pro-inflammatory activation of human PBMCs is better controlled by the recombinant version of AAT than the human plasma-derived AAT used here. Considering the increasing clinical interest in AAT therapy as useful to ameliorate the hyper-inflammation seen during COVID-19 infection, different AAT preparations require careful evaluation."

Journal • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CXCL8 • IL1B • IL6 • TNFA

Respreeza® Self-administration and Learning Program (AmAREtTI Study) (clinicaltrials.gov) - P=N/A; N=60; Recruiting; Sponsor: CSL Behring; Trial completion date: Dec 2022 ➔ Mar 2023; Trial primary completion date: Dec 2022 ➔ Mar 2023

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

Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β. (PubMed, Pulm Pharmacol Ther) - "As anti-inflammatory functions of AAT are of increasing clinical interest, we compared the potential of two widely used AAT preparations, Prolastin® and Respreeza®, to inhibit the ATP-induced release of IL-1β using human monocytic U937 cells. Our data suggest that the anti-inflammatory potential and the anti-protease function of AAT can be fully uncoupled. In the light of the increasing clinical interest in anti-inflammatory functions of AAT, commercial AAT preparations should be carefully reinvestigated and optimized to preserve the dual anti-protease and anti-inflammatory activity of native AAT."

Journal • Alpha-1 Antitrypsin Deficiency • Inflammation • Respiratory Diseases • ELANE • IL1B