Prolastin (alpha-1 antitrypsin inhibitor) / Grifols - LARVOL DELTA

Characteristics of patients in a community hospital-based COPD clinic (ERS 2025) - "Table 1 (mean±SD) Age (yrs) 64.5±6.7 Male % 68.5 Smokers (active/former) % 28.1/71.9 BMI kg/m 2 25.6±5.1 Charlson 3.76 mMRC 1.9 CAT 16.5 BODE 3.7 Table 2 (%) OSA/Bronchiectasis/Asthma/ILD 21.4/11.2/5.6/1.1 AATD/Prolastin treat... Our COPD clinic attended patients with high complexity and severity. A high prevalence of exacerbating and symptomatic patients was observed. The assessment of these data will allow the design of specific care strategies for these populations."

Clinical • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • LAMA2

A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study) (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

New P2 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL5

A Case of COVID-19 and Community-acquired Pneumonia in Alpha-1 Antitrypsin Deficiency (ATS 2025) - "The patient was started on Lactulose for hyperammonemia and altered mental status...She is on home Prolastin and on the list for lung and liver transplants... We describe COVID-19 and community-acquired pneumonia in a patient with AATD with severe emphysema and cirrhosis. Aggressive treatment of this patient's comorbidities led to her recovery, but many may not be as fortunate as in AATD; COVID-19 usually presents with severe symptoms and complications. Early identification and treatment are key to reducing rural and community hospital mortality."

Clinical • Alpha-1 Antitrypsin Deficiency • Cardiovascular • Chronic Obstructive Pulmonary Disease • Cough • Fibrosis • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases • ALK • ELANE

Unusual Inheritance Pattern of Alpha-1 Antitrypsin Deficiency: A Case Report of Four ZZ Phenotype Siblings From MZ Carrier Parents (ATS 2025) - "Serum alpha-1 antitrypsin levels were low, and liver function tests revealed elevated enzymes, prompting a hepatology referral and he is pending Prolastin infusions to manage his A1AT...Reporting this case calls for further research to explore these factors and emphasizes the importance of nuanced genetic counseling in A1AT deficiency. Enhanced awareness of this condition's varied presentation may shape future approaches to genetic predication and clinical expectations for A1AT inheritance."

Case report • Clinical • Alpha-1 Antitrypsin Deficiency • Fatigue • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Novel Coronavirus Disease • Obstructive Sleep Apnea • Pulmonary Disease • Respiratory Diseases • Sleep Disorder

THE QUADRUPPLE THREAT: UNRAVELING THE COMPLEXITIES OF ALPHA-1 ANTITRYPSIN DEFICIENCY (CHEST 2024) - "Treatment was initiated with AAT supplementation (Prolastin), COPD management including a umeclidinium bromide/vilanterol inhaler, supplemental oxygen, and pulmonary rehabilitation, which markedly improved her symptoms and pulmonary function. This case highlights the rare and unusual manifestations of AATD in a single patient, emphasizing the potential for late-life diagnosis and the increased risk of lung cancer, sinusitis, and iatrogenic pneumothorax associated with the condition."

Alpha-1 Antitrypsin Deficiency • Asthma • Bronchiectasis • Cardiovascular • Chronic Obstructive Pulmonary Disease • Cough • Genetic Disorders • Hepatology • Hypertension • Immunology • Lung Cancer • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • Solid Tumor • Squamous Cell Carcinoma • Vasculitis • SERPINA1

EFFICACY OF ALPHA1-ANTITRYPSIN AUGMENTATION THERAPY IN A GROUP OF PATIENTS WITH ALPHA1-ANTITRYPSIN DEFICIENCY DUE TO RARE VARIANTS (CHEST 2024) - "Patients underwent intravenous Human Alpha1 proteinase inibithor (Prolastin®) 60 ug/kg a week; treatment duration ranged from 3 to 8 years... Augmentatio therapy in patient affect by AATD and rare genotype defect, in our casistic, allows a significant reduction of respiratory exacerbations and respiratory symptoms with an excellent safety profile CLINICAL IMPLICATIONS: SERPINA 1 has a large spectrum of rare mutations, in many cases pathogenic and is important implementing the laboratories capacity of detecting the low frequency variants and not only the common deficiency alleles (S and Z). The AT could be effective in subjects with clinical manifestation of AATD and rare deciciency alleles. This point is very important to avoid late or inaccurate diagnosis in this rare (but not so rare) condition when an effective treatment is possible."

Clinical • Alpha-1 Antitrypsin Deficiency • Bronchiectasis • Hepatology • Inflammation • Pulmonary Disease • Respiratory Diseases • SERPINA1

α1-Antitrypsin regulates CXCR2 surface expression in human neutrophils via IL-8 release and expression (ERS 2024) - "Isolated human blood neutrophils were treated with AAT (Prolastin, 1 mg/ml) and/or IL8 (50 ng/ml) and/or lipopolysaccharide (LPS, 10 ng/ml) for 1, 4 and 24h...Finally at 24h, AAT by itself reduced IL8 mRNA expression. Our data show that exogenously added AAT regulates CXCR2 expression in neutrophils by inducing time-dependent changes in IL8 release and expression."

Critical care • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CXCL8 • CXCR1 • CXCR2

Patterns in Patient and Provider Characteristics Over Time Among Patients Initiating Alpha-1 Proteinase Inhibitors (ATS 2024) - "The study provides insights into the real-world clinical practice of A1PI administration in the United States. Additional research is needed to better identify existing barriers that delay or hinder care delivery and management."

Clinical • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Immunology • Inflammation • Respiratory Diseases

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

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

Pharmacokinetics and Biochemical Efficacy of an α-Proteinase Inhibitor (Aralast NP) in α-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis. (PubMed, Pulm Ther) - P1, P4 | "These retrospective analyses provide robust evidence that Aralast NP has biochemical efficacy and PK comparable to that of Aralast and Prolastin, supporting the use of any of these A1PI products for the treatment of patients with AATD."

Journal • PK/PD data • Retrospective data • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology

Impact of COVID-19 pandemic on information management and adherence to replacement therapy with AAT of patients with alpha-1 antitrypsin deficiency (AATM) (PubMed, Pneumologie) - "These survey results suggest that AATD patients are well-informed about the risks of COVID-19 with their condition and practised self-protection measures. This may have resulted in an COVID-19 infection rate lower than the general population. Although respondents were concerned about exposure to COVID-19 in their doctor's office or clinic, very few discontinued therapy even temporarily."

Journal • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Alpha-1 Antitrypsin for ARDS Secondary to Severe COVID-19 (ATS 2022) - "In addition to its anti-protease role, alpha-1 antitrypsin (AAT) is a potent immunomodulator, regulating the production and activity of several key pro-inflammatory cytokines. We conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of plasma-purified AAT (Prolastin, Grifols Pharmaceuticals) for ARDS secondary to severe COVID-19... In patients with COVID-19 and moderate-to-severe ARDS, treatment with IV AAT was safe, feasible and biochemically efficacious. The data support progression to a large phase 3 trial focusing on clinical endpoints, and prompt further investigation of AAT as an anti-inflammatory therapeutic."

Clinical • Acute Respiratory Distress Syndrome • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • CXCL8 • IL10 • IL1B • IL6 • TNFRSF1A

Severe Hyperinflation of Ipsilateral Lobes After Bronchoscopic Lung Volume Reduction Surgery (ATS 2022) - "She was already on maximal medical therapy for emphysema and prolastin infusion...It is also not known if these patients pose a higher risk for pneumothorax at baseline and should additional BLVRS be offered to these patients. This patient has worsening shortness of breath with decreased exercise tolerance and has been referred for lung transplant."

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

Increased Circulating Alpha-1 Antitrypsin Confers a Short- and Long-Term Survival Benefit in Acute Respiratory Distress Syndrome (ATS 2022) - "In conclusion, increased AAT in plasma is associated with better outcomes in ARDS. IV Prolastin® attenuated preclinical pneumonia induced ARDS and offers further evidence for supplementation of AAT in ARDS."

Acute Respiratory Distress Syndrome • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • CXCL8 • ELANE • IL6

Comparative biochemical efficacy analysis of an alpha-proteinase inhibitor (Glassia®) in patients with alpha-1 antitrypsin deficiency. (PubMed, Pulm Pharmacol Ther) - P2/3 | "For functional A1PI, the GMR (90% CI) was 98.7 (92.5-105.4) for baseline corrected and 107.8% (102.3-113.5) for uncorrected concentrations. In conclusion, the biochemical efficacy of Glassia using the endpoints of plasma antigenic and functional A1PI trough concentrations at steady state was comparable with Prolastin in patients with AATD."

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

A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for acute respiratory distress syndrome secondary to COVID-19. (PubMed, Med (N Y)) - P2 | "Patients (n=36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120mg/kg), or AAT once followed by weekly placebo...In patients with COVID-19 and moderate-to-severe ARDS, treatment with IV AAT was safe, feasible and biochemically efficacious. The data support progression to a phase 3 trial, and prompt further investigation of AAT as an anti-inflammatory therapeutic."

Clinical • Journal • Acute Respiratory Distress Syndrome • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL10 • IL1B • IL6

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

α1-Antitrypsin A treatment attenuates neutrophil elastase accumulation and enhances insulin sensitivity in adipose tissue of mice fed a high-fat diet. (PubMed, Am J Physiol Endocrinol Metab) - "Male C57Bl/6j mice fed a chow or a high fat diet (HFD) were randomized to receive 3x weekly i.p injections of either Prolastin (human A1AT; 2mg) or vehicle (PBS) for 10 weeks...Furthermore, PDGF mediated p-Akt activation and glucose uptake (which is independent of IRS-1) was not affected by recombinant NE treatment. Collectively, our findings suggest that NE infiltration of WAT during metabolic overload contributes to insulin-resistance by impairing insulin-induced IRS-1 signaling."

Journal • Preclinical • Diabetes • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • AAT • ELANE

Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19 (clinicaltrials.gov) - P2; N=100; Completed; Sponsor: Instituto Grifols, S.A.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • CRP • PCR

[VIRTUAL] Therapeutic Effects of Alpha 1 Antitrypsin Supplementation in Preclinical Acute Respiratory Distress Syndrome (ATS 2021) - "In conclusion, increased AAT in plasma is associated with better outcomes in ARDS and patients with concomitant AATD may be at a disadvantage. IV Prolastin® attenuated preclinical pneumonia induced ARDS and offers further evidence for supplementation of AAT in ARDS."

Preclinical • Acute Respiratory Distress Syndrome • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • AAT • ELANE • TNFA

Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19 (clinicaltrials.gov) - P2; N=100; Active, not recruiting; Sponsor: Instituto Grifols, S.A.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • CRP • PCR

A randomised, double-blind, placebo-controlled, pilot trial of intravenous plasma purified alpha-1 antitrypsin for SARS-CoV-2-induced Acute Respiratory Distress Syndrome: a structured summary of a study protocol for a randomised, controlled trial. (PubMed, Trials) - P2 | "The primary objective is to demonstrate that, in patients with PCR-confirmed SARS-CoV-2 resulting in Acute Respiratory Distress Syndrome (ARDS), administration of 120mg/kg of body weight of intravenous Prolastin®(plasma-purified alpha-1 antitrypsin) reduces circulating plasma levels of interleukin-6 (IL-6)...In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2)."

Clinical • Journal • Acute Kidney Injury • Acute Respiratory Distress Syndrome • Cardiovascular • Chronic Kidney Disease • Critical care • Genetic Disorders • Hepatology • Hypertension • Infectious Disease • Nephrology • Non-melanoma Skin Cancer • Novel Coronavirus Disease • Oncology • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Skin Cancer • Solid Tumor • AAT • CXCL8 • IL10 • IL1B • IL6 • TNFA

Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19 (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: Instituto Grifols, S.A.

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • CRP • PCR

Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19 (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: Instituto Grifols, S.A.; Trial completion date: Nov 2020 ➔ Apr 2021; Trial primary completion date: Nov 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • CRP • PCR