Naglazyme (galsulfase) / AnGes MG, BioMarin - LARVOL DELTA

Carpal Tunnel Syndrome Attributed to Medication Use: A Pharmacovigilance Study. (PubMed, Cureus) - "Several drugs were disproportionately associated with CTS in the FAERS database, including enzyme replacement therapies (ERTs), aromatase inhibitors, bisphosphonates, growth hormone (GH)-releasing factor analogs, GHB, rofecoxib, and tafamidis. These findings highlight the critical need for increased vigilance and monitoring of new-onset or worsening CTS in high-risk populations prescribed the aforementioned medications. Clinicians should carefully scrutinize pharmacological history when evaluating patients in this context."

Adverse events • Journal • Musculoskeletal Pain • Pain

Long-term enzyme replacement therapy: Findings from the mucopolysaccharidosis VI clinical surveillance program after 15 years follow-up. (PubMed, Mol Genet Metab) - "Data collected in the CSP over 15 years provide real-world evidence for sustained improvements in endurance and pulmonary function among patients with MPS VI treated with ERT, with no new safety concerns identified. These results further support and confirm observations from the clinical trials and previous findings from the CSP."

Journal

Efficacy of different treatment strategies in patients with mucopolysaccharidosis: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, Orphanet J Rare Dis) - "In MPS IV, 6-min walking test (6MWT) (40.82, 95% CI[16.19, 64.92]) and 3-min stair climb test (3MSCT) (16.07, 95% CI[12.16, 21.62]) were significantly increased in patients who took elosulfase alfa at a dose of 4.0 mg/kg/week compared with the placebo group. In MPS VI, recombinant human arylsulfatase B (rhASB) and galsulfase (1.0 mg/kg/week) significantly reduced uGAG aggregation compared with the placebo group (-217, 95% CI[-258, -176]) and galsulfase (2.0 mg/kg/week) group (-286.5, 95% CI[-436.5, -136.5]), respectively...ERT alleviated symptoms to some extent, but current evidence was insufficient. Hence, further evidence from large-sample RCT is needed."

Journal • Retrospective data • Review

Histopathological and Clinical-Genetic Analysis of Corneal Specimens in Maroteaux-Lamy Syndrome. (PubMed, Cornea) - "The study highlights the alterations in various corneal layers, which have seldom been reported on Maroteaux-Lamy syndrome. Nonetheless, the GAG deposits identified and the changes in Bowman layer align with the literature. PK temporarily improved corneal clarity. However, long-term visual outcomes were poor because of optic nerve damage. Early diagnosis and multidisciplinary management are essential to improve outcomes."

Journal • Lysosomal Storage Diseases • Metabolic Disorders • Ophthalmology • Rare Diseases • Transplantation

MUCOPOLYSACCHARIDOSES IN ADULT PATIENTS – ONE CENTRE EXPERIENCE (SSIEM 2024) - "ERT depended on the MPS`s type and included laronidase, idursulfase, elosulfase alfa, and galsulfase. Our patients treated with ERT have good compliance and almost no significant progression of their diseases in ten-year follow-up."

Clinical • Alzheimer's Disease • Atrial Fibrillation • Cardiovascular • Cognitive Disorders • Hurler Syndrome • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Musculoskeletal Diseases • Rare Diseases • Respiratory Diseases

Real-world pharmacovigilance analysis of galsulfase: a study based on the FDA adverse event reporting system (FAERS) database. (PubMed, Front Pharmacol) - "The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment."

Adverse events • Journal • Real-world • Real-world evidence • Glomerulonephritis • Infectious Disease • Lupus Nephritis • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Rare Diseases • Urology

Unveiling the role of novel carbohydrate-binding modules in laminarin interaction of multimodular proteins from marine Bacteroidota during phytoplankton blooms. (PubMed, Environ Microbiol) - "Exploration of bacterial metagenome-assembled genomes (MAGs) from phytoplankton blooms in the North Sea showed that both laminarin-binding CBM families are widespread among marine Bacteroidota. The high protein abundance of CBM102- and CBM103-containing proteins during phytoplankton blooms further emphasizes their significance in marine laminarin utilization."

Journal

Purification of extracellular vesicles produced by filarial parasites for proteomic detection of biomarker candidates in human plasma (ASTMH 2023) - "Two 14-3-3 B. malayi homologs were detected in the gerbil (Bm4259 and Bm10299)...From these experiments, it is shown that vesicles can be detected in plasma from patients with high infection of parasite. With this, new biomarker candidates for both LF and loiasis have been identified and will be explored in future work."

Biomarker • Infectious Disease

The First Managed Entry Agreements Based on Health Technology Assessment Approved in Ukraine: Analysis and Future Perspectives (ISPOR 2023) - "So, henceforth patients in Ukraine will get an improved access to 10 medicines for rare diseases: risdiplam, plasma-derived C1-esterase inhibitor, factor VIII inhibitor bypassing activity, alglucosidase alfa, imiglucerase, velaglucerase alfa, elosulfase alfa, galsulfase, idursulfase, laronidase. Conclusion of the first MEAs based on HTA is an effective tool to improve patients' access to innovative medicines and make efficient resource allocation for public payer expenditures in Ukraine."

Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

A Study Evaluating the Safety, Tolerance and Anti-tumor Activity of HBM1020 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: Harbour BioMed US, Inc.

Metastases • New P1 trial • Colorectal Adenocarcinoma • Oncology • Solid Tumor

IUERT: In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of California, San Francisco | Trial completion date: Apr 2032 ➔ Jul 2032 | Trial primary completion date: Apr 2031 ➔ Jul 2031

Trial completion date • Trial primary completion date • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Superfluid Density in Conventional Superconductors: From Clean to Strongly Disordered. (PubMed, J Phys Condens Matter) - "B $bm{102}$, 024514 (2020)] has been reformulated to separate out the generally used so-called `dirty-limit' term and an additional term. We use this new expression for making an extensive comparison with previously published experimental data and show that the former, generally used, term is {it not} sufficient for analyzing these results. We point out that consequently, there is a large regime (disordered superconductors with moderate to no disorder) where theoretical predictions need to be confronted with experiment."

Journal • CNS Disorders

Novel chorioretinal findings in two siblings with mucopolysaccharidosis type VI. (PubMed, Ophthalmic Genet) - "To describe and compare the systemic and ocular findings in two siblings with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome), one treated with recombinant galsulfase, and one who was untreated...These two siblings with mucopolysaccharidosis type VI, one treated and one untreated, displayed variable levels of systemic, corneal, and chorioretinal involvement in their disease Further studies of choroidal changes in MPS VI may prove useful as a biomarker of ocular response to treatment outside the blood-retina barrier. Both patients have provided written consent to publish case details."

Journal • Ophthalmology • Retinal Disorders

Fifteen years of enzyme replacement therapy for mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): a case report. (PubMed, J Med Case Rep) - "Although enzyme replacement therapy did not prevent the main signs of mucopolysaccharidosis VI, it slowed their progression. Additionally, enzyme replacement therapy was associated with a longer survival compared with the untreated affected sibling. Taken together, the results indicate that enzyme replacement therapy positively modified the course of the disease."

Journal • Musculoskeletal Pain

Utility of galsulfase skin testing in the evaluation of infusion reactions (AAAAI 2022) - "A 5 year-old girl with mucopolysaccharidosis-VI developed a reaction to intravenous galsulfase characterized by fever, tachycardia, flushing, facial rash, wheezing and respiratory distress managed with epinephrine. The simplified, shorter protocol improved patient quality of life and reduced health care resource utilization. Skin testing is a valuable tool in the evaluation and management of galsulfase reactions."

Cardiovascular • Immunology

Effectiveness of drug postmarketing all-case surveillance as a safety measure in Japan. (PubMed, Ther Adv Drug Saf) - "Naglazyme (galsulfase) is a case where the PMACS-like studies have been required in each region...Meanwhile, some drugs were highlighted as potential factors for better application of the obligation.: According to these results, the obligation should be imposed on a limited number of drugs by focusing not on dosing experience in Japan but on safety (not efficacy) data collection, necessity of distribution control, and/or collection of case details for drugs with a limited treated population. The obligation also has the potential to be utilized in the EU and the United States, as their regulatory frameworks are acceptable for the obligation."

Clinical • Journal • P4 data

Clinical and event-based outcomes of patients with mucopolysaccharidosis VI receiving enzyme replacement therapy in Turkey: a case series. (PubMed, Orphanet J Rare Dis) - "This case series shows the high disease burden of the MPS VI population in Turkey and provides a unique insight into their clinical journey based on real-life clinical and event-based data collected before and after initiation of ERT."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Hurler Syndrome • Immunology • Infectious Disease • Obstructive Sleep Apnea • Ophthalmology • Orthopedics • Otorhinolaryngology • Pediatrics • Psychiatry • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Urinary Incontinence • Urology • MRI

Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type VI. (PubMed, Cochrane Database Syst Rev) - "We are also uncertain whether there are any differences between treatment groups in relation to cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects. Further studies are needed to obtain more information on the long-term effectiveness and safety of ERT with galsulfase."

Journal • Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Heart Failure • Immunology • Metabolic Disorders • Obstructive Sleep Apnea • Ophthalmology • Orthopedics • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Rheumatology • Sinusitis • Sleep Apnea • Sleep Disorder

IUERT: In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: University of California, San Francisco; Not yet recruiting ➔ Recruiting

Enrollment open • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Long-term outcomes of patients with mucopolysaccharidosis VI treated with galsulfase enzyme replacement therapy since infancy. (PubMed, Mol Genet Metab) - P4 | "Very early and continuous ERT appears to slow down the clinical course of MPS VI, as shown by preservation of endurance, functional dexterity, and several fine and gross motor competencies after 7.7-9.8 years of treatment, and less growth impairment or progression of cardiac disease than could be expected based on the patients' classical phenotype. ERT does not seem to prevent progression of skeletal or eye disease in the long term."

Clinical • Journal • Heart Failure • Ocular Infections • Ophthalmology • Orthopedics

Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: A resurvey study. (PubMed, Mol Genet Metab) - "Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth...Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT."

Clinical • Journal • CNS Disorders • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Obstructive Sleep Apnea • Ophthalmology • Orthopedics • Pneumonia • Rare Diseases • Respiratory Diseases • Sleep Apnea • Sleep Disorder

IUERT: In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: University of California, San Francisco; Initiation date: Dec 2020 ➔ Mar 2021

Trial initiation date • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Naglazyme After Allo Transplant for Maroteaux-Lamy Syndrome (clinicaltrials.gov) - P=N/A; N=1; Terminated; Sponsor: Masonic Cancer Center, University of Minnesota; Active, not recruiting ➔ Terminated; Slow accrual

Trial termination • Transplantation

[VIRTUAL] Implication of Approval UNDER Exceptional Circumstances on Reimbursement in France (ISPOR-EU 2020) - "Among them, IAB was rated as 1 (major) for OrphacolÒ, 2 (important) for StrensiqÒ, AtrianceÒ, ElapraseÒ, and EvoltraÒ, 3 (moderate) for NaglazymeÒ and BrineuraÒ, 4 (minor) for MyaleptaÒ, QarzibaÒ, LojuxtaÒ, VyndaqelÒ, and VedropÒ, and 5 (weak) for ObizurÒ. Most of these drugs (84,6%) had non-comparative trials and limited/lack of evidence on clinical efficacy benefit.CONCLUSIONSEven with limited clinical evidence, HAS issued positive recommendations for reimbursement of drugs approved under EC, allowing faster patient access to drugs with no available alternatives and high unmet need. In France, single-arm trial and limited efficacy data does not seem an obstacle for reimbursement of these promising drugs for untreated diseases."

Reimbursement • Metabolic Disorders • Oncology • Pediatrics

IUERT: In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (clinicaltrials.gov) - P1; N=10; Not yet recruiting; Sponsor: University of California, San Francisco

New P1 trial • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases