Elelyso (taliglucerase alfa) / Pfizer - LARVOL DELTA

Plant molecular farming: a promising frontier for orphan drug production. (PubMed, Biotechnol Lett) - "The FDA approval of plant-derived proteins for the treatment of Gaucher disease (Elelyso) and Fabry disease (Elfabrio) highlights the potential of plant-based expression systems for the development of suitable drugs targeting niche and orphan diseases. This review examines the potential of the plant system in producing orphan drugs and also highlights the opportunities and challenges related to orphan drug manufacturing."

Journal • Orphan drug • Review • Fabry Disease • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Rare Diseases

ORPHAN DRUGS IN ALZHEIMER'S DISEASE: CROSSROAD OF AMYLOID PATHOLOGY AND LYSOSOMAL STORAGE DISEASES (ADPD 2025) - "To test this hypothesis the effects of cerliponase alfa and taliglucerase alfa on A β accumulation in mouse hippocampal neurons (HT -22 neuronal cells) exposed to fAβ1-42 (a toxic fragment of full -length A β) and markers of autophagy -lysosome pathway related to AD were investigated. Therefore, we suggest that these orphan drugs could be considered promising novel therapeutics for neurodegenerative diseases in which autophagy pathways are impaired."

Alzheimer's Disease • CNS Disorders • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • ATG5 • GBA1 • mTOR

BRAZILIAN EXPERIENCE WITH TALIGLUCERASE ALFA FOR GAUCHER'S DISEASE: DESCRIPTIVE RESULTS (SSIEM 2024) - "This analysis suggests that TA therapy is a safe and effective treatment option for patients with type 1 GD, including for patients switched from other ERT."

Cough • Dermatology • Gaucher Disease • Immunology • Metabolic Disorders • Musculoskeletal Pain • Pain • Pediatrics • Rare Diseases • Respiratory Diseases • Urticaria

Taliglucerase alfa in the longterm treatment of children and adolescents with type 1 Gaucher disease: the Albanian experience. (PubMed, Front Pediatr) - "Out of the 1,301 total administrations, our patients reported only 37 (2.8%) infusion-related adverse events which were mild and transitory. Taliglucerase alfa exhibits good efficacy and a safe profile in the treatment of children and adolescents with Type 1 Gaucher disease."

Journal • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

Green Biologics: Harnessing the Power of Plants to Produce Pharmaceuticals. (PubMed, Int J Mol Sci) - "Plants have proved that they can produce life-saving therapeutic proteins (Elelyso™-Gaucher's disease treatment, ZMapp™-anti-Ebola monoclonal antibodies, seasonal flu vaccine, Covifenz™-SARS-CoV-2 virus-like particle vaccine); however, some of these therapeutic proteins are difficult to bring to market, which leads to serious difficulties for the manufacturing companies...The versatility of plant-derived biologics across diverse fields, such as human and animal health, industry, and agriculture, is emphasized. This review also meticulously examines regulatory considerations specific to plant-derived biologics, shedding light on the disparities faced compared to biologics produced in other systems."

Journal • Review • Ebola Virus Disease • Gaucher Disease • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

Skeletal Manifestations, Bone Pain, and BMD Changes in Albanian Type 1 Gaucher Patients Treated with Taliglucerase Alfa. (PubMed, J Osteoporos) - "Bone pain has gradually improved in all patients. Also, BMD values have been enhanced over six years of treatment, especially in children."

Journal • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Musculoskeletal Pain • Pain • Type 1 Gaucher Disease

A Multicenter, Safety and Efficacy Study of Taliglucerase Alfa in Subjects With Type 3 Gaucher Disease (clinicaltrials.gov) - P4 | N=14 | Completed | Sponsor: Ari Zimran | Active, not recruiting ➔ Completed

Trial completion • Gaucher Disease • Genetic Disorders • Metabolic Disorders

Real-World Experiences with Taliglucerase Alfa Home Infusions for Patients with Gaucher Disease: A Global Cohort Study. (PubMed, J Clin Med) - "Twelve serious AEs in five separate case reports were considered treatment related: one case of chest discomfort/pain and hypertension and one case of erythema associated with a toe blister, for which causality could not be excluded; pain in extremity; projectile vomiting and chills, alongside excessive eye blinking; and an infusion-related AE (pruritus). In conclusion, this real-life global study demonstrated that taliglucerase alfa home infusions are safe with high compliance rates."

Journal • Real-world • Real-world evidence • Cardiovascular • Dermatology • Gaucher Disease • Genetic Disorders • Hypertension • Metabolic Disorders • Pain • Pruritus

An Efficacy and Safety Study of AVR-RD-02 Compared to Enzyme Replacement Therapy for Treatment of Gaucher Disease Type 3 (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: AVROBIO | N=40 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Gene therapy • Trial withdrawal • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders

An Efficacy and Safety Study of AVR-RD-02 Compared to Enzyme Replacement Therapy for Treatment of Gaucher Disease Type 3 (clinicaltrials.gov) - P2/3 | N=40 | Not yet recruiting | Sponsor: AVROBIO

Gene therapy • New P2/3 trial • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders

The Bone Biomarker of Quantitative Chemical Shift Imaging in Patients with Type 1 Gaucher Disease Receiving Low-Dose Long-Term Enzyme Replacement Therapy. (PubMed, J Clin Med) - "A minority of such patients with suboptimal bone response require therapeutic change. The next phase of the study will address the effect of switching to taliglucerase alfa on bone status for patients with less than optimal QCSI scores (<0.30)."

Biomarker • Journal • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

Open-Label, Expanded Access Study of Taliglucerase Alfa in Patients with Gaucher Disease Requiring Enzyme Replacement Therapy (ASH 2018) - P=N/A; "In treatment-naïve patients, mean hemoglobin concentration and platelet counts increased. In conclusion, taliglucerase alfa was well tolerated for up to 33 months of treatment and demonstrated a durable therapeutic effect, as evidenced by stable or improved hemoglobin concentration and platelet counts in this expanded access study."

Clinical • Biosimilar • Type 1 Gaucher Disease

Budget Impact Analysis of Gaucher Disease Pharmacologic Treatment in Colombia (ISPOR-EU 2022) - "This study developed a Budget Impact Analysis of including Enzyme Replacement Therapy - ERT (Imiglucerase, Taliglucerase, Velaglucerase) and Substrate Reduction Therapy - SRT (Eliglustat) for type I Gaucher Disease (GDI) from the health system perspective over a 3-year time horizon in enrolled Colombian population. Therapy of choice and its frequency affect the most on budget impact in the health system. Almost all GDI cost burden is due to medications and treatment mix."

HEOR • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Rare Diseases • Type 1 Gaucher Disease

Assessing the Impact of Elelyso on Bone Involvement Currently Treated With Other ERTs (clinicaltrials.gov) - P=N/A | N=30 | Completed | Sponsor: Shaare Zedek Medical Center | Unknown status ➔ Completed

Trial completion • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

A Multicenter, Safety and Efficacy Study of Taliglucerase Alfa in Subjects With Type 3 Gaucher Disease (clinicaltrials.gov) - P4 | N=14 | Active, not recruiting | Sponsor: Ari Zimran | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2022 ➔ Jul 2023

Enrollment closed • Trial primary completion date • Gaucher Disease • Genetic Disorders • Metabolic Disorders

A Systematic Review and Meta-analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease. (PubMed, Ann Pharmacother) - "The studies evaluated imiglucerase, velaglucerase alfa, taliglucerase alfa, miglustat, and eliglustat...Based on the assessed evidence, miglustat did not achieved expressive results. However, all evidence should be interpreted considering its limitations and does not replace well-conducted randomized trials."

Journal • Observational data • Review • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Rare Diseases

The budget impact of enzyme replacement therapy in type 1 Gaucher disease in the United States. (PubMed, J Med Econ) - "Across analyses, cost savings were realized with velaglucerase alfa compared with imiglucerase ($115,909) and taliglucerase alfa ($80,401)...The per-member per-month costs decreased by $0.0241 across years 1-3. BIM results show that increased velaglucerase alfa uptake for GD1 treatment is cost saving for US health plans."

HEOR • Journal • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

A Multicenter, Safety and Efficacy Study of Taliglucerase Alfa in Subjects With Type 3 Gaucher Disease (clinicaltrials.gov) - P4 | N=15 | Recruiting | Sponsor: Ari Zimran | Trial completion date: Aug 2022 ➔ Aug 2023

Trial completion date • Gaucher Disease • Genetic Disorders • Metabolic Disorders

Systematic Review and Meta-Analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease: Focus on Hematological Parameters (ISPOR 2022) - "Several meta-analyses were conducted for each drug: imiglucerase (6 months to 5 years), velaglucerase alfa (6 months to 7 years), taliglucerase alfa (6 months to 5 years), miglustat (6 months to 4 years), and eliglustat (6 months to 9 years). long-term results showed that ERTs are effective as treatment in both naïve and experienced patients. Miglustat did not significantly improve hemoglobin values in naïve patients and resulted in the decrease of platelet levels in experienced patients. All this evidence should be interpreted considering its limitations and does not replace a well conducted randomized trial."

Observational data • Review • Gaucher Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Safety and effectiveness of taliglucerase alfa in patients with Gaucher disease: an interim analysis of real-world data from a multinational drug registry (TALIAS). (PubMed, Orphanet J Rare Dis) - "The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa."

Journal • Real-world evidence • Gaucher Disease • Genetic Disorders • Metabolic Disorders

2022 DIC Wang award lecture: Plants as molecular foundries: From earth to deep space (ACS-Sp 2022) - "Although the first FDA-approved human therapeutic made in plant cell culture was introduced just ten years ago (ElelysoTM made in transgenic carrot cultures), plant cell culture offers a number of advantages: simple, chemically-defined, low cost animal component-free medium, the ability to produce complex glycoproteins, potential for long-term operation, and inability to propagate mammalian viruses. However, these systems are not without their own challenges. This presentation will describe some of the unique challenges encountered when using plants as molecular foundries, as well as our group’s research over the years to increase productivity, product quality, and production speed, with applications ranging from medical countermeasures for biodefense on Earth to molecular pharming on Mars."

[VIRTUAL] DEFICIENCY OF BETAGLYCOSIDASE AND GLYCOLIPIDIO ACCUMULATION IN INDIVIDUALS WITH GAUCHER'S DISEASE IN A REGION OF NORTHEASTERN BRAZIL (HEMO 2021) - "Introduction First described by the French physician Philippe Charles Ernest Gaucher, in 1882, Gaucher disease is a genetic disorder resulting from a deficiency of the enzyme betaglycocerebrosidase, or betaglucosidase, whose function is to digest glucocerebroside, a type of fat resulting from cell waste that die every day and are replaced by new ones. Its treatment is done by Enzymatic Replacement Therapy, being applied through weekly or biweekly infusions for the replacement of the enzyme Beta-Glucoserebrosidase. There are reports of the development of antibodies in individuals treated with the use of Imiglucerase infusions with an approximate percentage of 10-15%. Early diagnosis and correct treatment of drug infusions with correct frequency lead to a reduction in disease symptoms and improvement in the patient's quality of life.Objective Assess the quantity of infusions of Enzyme Replacement drugs Imiglucerase and Taliglucerase used for the..."

Clinical • Gaucher Disease • Metabolic Disorders • Rare Diseases

Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines. (PubMed, Vaccines (Basel)) - "The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far."

Journal • Review • Gaucher Disease • Genetic Disorders • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

Impact of Long-Term Enzyme Replacement Therapy on Glucosylsphingosine (Lyso-Gb1) Values in Patients with Type 1 Gaucher Disease: Statistical Models for Comparing Three Enzymatic Formulations. (PubMed, Int J Mol Sci) - "A total of 135 adult patients (77 (57%) female) with GD1, followed from July 2014 to March 2020 and treated with a single ERT (imiglucerase (n = 41, 30.4%), taliglucerase alfa (n = 21, 15.6%) and velaglucerase alfa (n = 73, 54.1%)), were included...A steeper and faster decrease of lyso-Gb1 levels was shown in velaglucerase alfa. Nevertheless, the differences between medications were not very large, and bigger numbers and more pretreatment data are required for more powerful conclusions."

Clinical • Journal • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

Cellular engineering of plant cells for improved therapeutic protein production. (PubMed, Plant Cell Rep) - "Over the past three decades, substantial progress has been made in improving the plant cell culture system, resulting in a few commercial success cases, such as taliglucerase alfa (Elelyso), the first FDA-approved recombinant pharmaceutical protein derived from plant cells...Modern molecular biology tools, in particular RNAi and the latest genome editing technology CRISPR/Cas9, have been used to modulate the genome of plant cells to create new cell lines that exhibit desired "traits" for producing therapeutic proteins. This review highlights the recent advances in cellular engineering of plant cells towards improved recombinant protein production, including creating cell lines with deficient protease levels or humanized glycosylation, and considers potential development in the future."

Journal • Review