Aldurazyme (laronidase) / BioMarin, Sanofi - LARVOL DELTA

Autologous human peripheral blood B cells genetically engineered to express human iduronidase: Results from a first-in-human clinical trial in subjects with mucopolysaccharidosis type I (MPS I) (ASGCT 2025) - "The first subject is a 25-year-old male who has been on enzyme replacement therapy (ERT; laronidase) for 13 years. These early results support both the dose escalation of ISP-001 to treat MPS I and the expansion of this new engineered B cell platform to treat other human diseases. Disease Focus of Abstract:Storage/Lysosomal Disorders"

Clinical • P1 data • Bone Marrow Transplantation • Hurler Syndrome • Orthopedics • Rare Diseases • IDUA

Two-year follow-up after drug desensitization in mucopolysaccharidosis. (PubMed, Orphanet J Rare Dis) - "The combined desensitization approach proved effective in conferring immunotolerance for at least one year in both MPS patients, also demonstrated by the negative skin tests in one patient. However, when immunotolerance to ERT is lost, omalizumab administration can be a valid option in restoring ERT."

Journal • Allergy • Hunter Syndrome • Hurler Syndrome • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH. (clinicaltrials.gov) - P=N/A | N=24 | Recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2025 ➔ Oct 2026 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Hurler Syndrome • Transplantation

NEUROBEHAVIOURAL AND SOMATIC IMPROVEMENTS OBSERVED IN MPS I PATIENTS TREATED WITH LEPUNAFUSP ALFA (JR-171): REPORT OF FOUR CASES. (SSIEM 2024) - "Along with the findings on the somatic efficacy of JR-171 in its phase 1/2 study, the observed neurobehavioural changes may suggest potential benefits of the drug on neuronopathy that requires further evaluation."

Clinical • Cardiomyopathy • Cardiovascular

HEMATOPOIETIC STEM CELL TRANSPLANT FOR MUCOPOLYSACCHARIDOSIS TYPE I - 3 YEARS FOLLOW-UP – CASE REPORT (SSIEM 2024) - "Enzyme replacement therapy (ERT) with laronidase was started at 14 months, followed by HSCT at 20 months... HSCT is currently the only therapeutic approach capable of modifying the course of neurocognitive disease in MPS I. Although HSCT was performed before the age of 2 years (Y) in our patient, his phenotype was severe, already with significant psychomotor delay at an early age. Neonatal screening for MPS I and earlier diagnosis would have allowed a better neurocognitive outcome in this case."

Case report • Clinical • Bone Marrow Transplantation • CNS Disorders • Cognitive Disorders • Developmental Disorders • Gastroenterology • Graft versus Host Disease • Hepatology • Hurler Syndrome • Immunology • Transplantation • IDUA

SAFETY AND EFFICACY OF LARONIDASE IN CHINESE PATIENTS WITH MUCOPOLYSACCHARIDOSIS TYPE I: A PHASE 4, SINGLE-ARM, OPEN-LABEL, MULTICENTER STUDY (SSIEM 2024) - P4 | "Laronidase reduced uGAG levels from baseline throughout the treatment period up to week 26, with a mean (SD) percentage change of -64.61% (26.90), 95% CI [-81.70%, -47.52%].Discussion/Conclusion Laronidase is safe and well-tolerated with no new safety signals, and reduces uGAG levels in Chinese MPS I patients. Palavras-chave : MPS I, ERT, laronidase, phase 4 study, Chinese"

Clinical • P4 data • Cardiovascular • Cough • Dermatology • Hematological Disorders • Hurler Syndrome • Hypertension • Hypotension • Immunology • Infectious Disease • Respiratory Diseases • Urticaria

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

SKELETAL FINDINGS IN PATIENTS WITH ATTENUATED MPS I RECEIVING LARONIDASE ENZYME REPLACEMENT THERAPY: DESCRIPTIVE DATA FROM THE MPS I REGISTRY (SSIEM 2024) - P | "Skeletal findings were prevalent in attenuated MPS I, often manifesting in late childhood or early adolescence. Further studies are warranted to explore the impact of treatment timing on skeletal development."

Clinical • Hurler Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Orthopedics • Rare Diseases • IDUA

Laronidase-loaded liposomes reach the brain and other hard-to-treat organs after noninvasive nasal administration. (PubMed, Int J Pharm) - "Nasal administration of complexes to MPS I mice resulted in significant increase in laronidase activity in the brain cortex, heart, lungs, kidneys, eyes, and serum. The overall results demonstrate the feasibility of nasal administration of laronidase-loaded liposomes to deliver enzyme in difficult-to-reach tissues, circumventing ERT issues and bringing hope as a potential treatment for MPS I."

Journal • Hurler Syndrome • IDUA

Efficacy and Safety of P046 (Laronidase-CinnaGen) Compared to Aldurazyme® in MPS I Patients (clinicaltrials.gov) - P3 | N=12 | Completed | Sponsor: Cinnagen

New P3 trial • Hurler Syndrome

A Case of Mucopolysaccharidosis Type 1 with Associated Papilledema Respondent to Therapy (AAN 2024) - "Design/NAA 14-year-old female with MPS type 1 (managed with once weekly laronidase infusions) was referred to child neurology clinic for optic nerve swelling. Optic nerve swelling in MPS disorders is common, but the pathophysiology remains unknown. True papilledema could play a role in the symptomatic presentation of optic nerve swelling and contribute to worsening visual acuity in these patients. Other potential factors for optic disc edema include deposition of glycosaminoglycans into the ganglion cells around the optic nerves and compression of the nerves due to glycosaminoglycan deposition in the surrounding tissues, causing pseudopapilledema."

Clinical • Hurler Syndrome • Otorhinolaryngology • Pain

Efficacy of a Combination Therapy with Laronidase and Genistein in Treating Mucopolysaccharidosis Type I in a Mouse Model. (PubMed, Int J Mol Sci) - "However, this therapy negated some laronidase benefits in the HCII-T levels. Importantly, the combination therapy improved the behavior of female mice with MPS I. These findings offer valuable insights for future research to optimize MPS I treatments."

Combination therapy • Journal • Preclinical • Hurler Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Study of the Effect of Aldurazyme® (Laronidase) Treatment on Lactation in Female Patients With Mucopolysaccharidosis I (MPS I) and Their Breastfed Infants (clinicaltrials.gov) - P4 | N=2 | Terminated | Sponsor: Genzyme, a Sanofi Company | Recruiting ➔ Terminated; Study was conducted to fulfill a post marketing commitment (PMC). FDA acknowledged closure of PMC.

Trial termination • Hurler Syndrome

Safety and Tolerability of a Stepwise Increased Starting Rate for Laronidase Infusion in Mucopolysaccharidoses Type 1H (MPS 1H) Patients (TCT-ASTCT-CIBMTR 2024) - "When given at maximum starting rate the infusion duration is reduced 20% to 3.125 hours. Given the safety and tolerability in this cohort, this approach could be considered to reduce infusion time burden for MPS 1H patients."

Clinical • Dermatology • Hurler Syndrome • Immunology • Pain • Pediatrics • Transplantation • Urticaria

HomERT: A Study to Assess the Safety of Myozyme® and of Aldurazyme® in Male and Female Participants of Any Age Group With Pompe Disease or With Mucopolysaccharidosis Type I (MPS I) in a Home-care Setting (clinicaltrials.gov) - P=N/A | N=57 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Hurler Syndrome • Pompe Disease • IDUA

α-L-iduronidase fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa) for mucopolysaccharidosis type I: A Phase 1/2 Trial. (PubMed, Mol Ther) - "Plasma drug concentration increased dose-dependently and reached its maximum approximately 4 hours after the end of drug administration. Decreased HS in the cerebrospinal fluid suggested successful delivery of JR-171 across the BBB, while suppressed urine and serum concentrations of the substrates indicated its somatic efficacy was comparable to that of laronidase."

Journal • P1/2 data • Bone Marrow Transplantation • Hurler Syndrome • Transplantation • IDUA

Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH. (clinicaltrials.gov) - P=N/A | N=24 | Recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Enrolling by invitation ➔ Recruiting

Enrollment status • Hurler Syndrome • Transplantation

China post-marketing surveillance (PMS) study of Aldurazyme® (clinicaltrialsregister.eu) - P4 | N=16 | Sponsor: Genzyme Europe B. V

New P4 trial • Metabolic Disorders

Safety outcomes and patients' preferences for home-based intravenous enzyme replacement therapy (ERT) in pompe disease and mucopolysaccharidosis type I (MPS I) disorder: COVID-19 and beyond. (PubMed, Orphanet J Rare Dis) - "Evidence of favorable safety profile, improved treatment compliance and personal satisfaction validates the use of ERT with laronidase and alglucosidase alfa as a strong candidate for home therapy."

Journal • Hurler Syndrome • Infectious Disease • Novel Coronavirus Disease • Pompe Disease • Respiratory Diseases

Survival, Cardiac, and Pulmonary Outcomes In Individuals with Attenuated MPS I Receiving Laronidase Enzyme Replacement Therapy: Data from The MPS I Registry (SSIEM 2023) - P=N/A | "MPS I Registry data suggest that laronidase stabilizes cardiac and pulmonary function in attenuated MPS I, and cardiac and respiratory-related events are the primary causes of early mortality. Ten- year survival after first treatment is high, and future studies are needed to determine if earlier diagnosis and treatment improve outcomes in attenuated MPS I."

Clinical • Hurler Syndrome • Pulmonary Disease • Respiratory Diseases

China Post-marketing Surveillance (PMS) Study of Aldurazyme® (clinicaltrials.gov) - P4 | N=12 | Completed | Sponsor: Genzyme, a Sanofi Company | Active, not recruiting ➔ Completed

Trial completion

Survival, Cardiac, and Pulmonary Outcomes In Individuals with Attenuated MPS I Receiving Laronidase Enzyme Replacement Therapy: Data from The MPS I Registry (SSIEM 2023) - No abstract available

Clinical

Survival, Cardiac, and Pulmonary Outcomes In Individuals with Attenuated MPS I Receiving Laronidase Enzyme Replacement Therapy: Data from The MPS I Registry (SSIEM 2023) - No abstract available

Clinical

Survival, Cardiac, and Pulmonary Outcomes In Individuals with Attenuated MPS I Receiving Laronidase Enzyme Replacement Therapy: Data from The MPS I Registry (SSIEM 2023) - No abstract available

Clinical

Survival, Cardiac, and Pulmonary Outcomes In Individuals with Attenuated MPS I Receiving Laronidase Enzyme Replacement Therapy: Data from The MPS I Registry (SSIEM 2023) - No abstract available

Clinical