recombinant human arylsulfatase A (TAK-611) / Takeda - LARVOL DELTA

Bifunctional Artificial Enzymes-Loaded Microgels With LOX- and CAT-Like Activities for Metabolic Reprogramming and Scarless Wound Repair. (PubMed, Adv Sci (Weinh)) - "Herein, a metabolism-regulating and inflammation-modulatory artificial enzyme, Metazyme, was developed, which exhibited dual lactate oxidase (LOX)-like and catalase (CAT)-like activities to oxidize lactate and decompose hydrogen peroxide (H2O2), enabling efficient oxygen recycling...In a rat full-thickness wound model in vivo, the MetaRgel significantly accelerated healing, enhanced granulation and collagen organization, and notably reduced glycolytic enzyme activity as well as the fibrotic marker α-smooth muscle actin (α-SMA) and hypoxia-inducible factor 1α (HIF-1α). The targeting of lactate-centered metabolic dysregulation with cascade artificial enzymes offers a promising approach to interrupt inflammation-metabolism-fibrosis crosstalk and promote scarless skin regeneration."

Journal • Fibrosis • Immunology • Inflammation • Metabolic Disorders • CAT • HIF1A • IL6 • PKM • TGFB1

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=24 | Enrolling by invitation | Sponsor: Shire | Trial primary completion date: Oct 2021 ➔ Oct 2023

Trial primary completion date • Metabolic Disorders

EMBOLDEN: A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: Shire | Trial completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Metabolic Disorders

EMBOLDEN: A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: Shire | Trial completion date: Mar 2025 ➔ Oct 2025

Trial completion date • Metabolic Disorders

EMBOLDEN: A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: Shire | Trial completion date: Aug 2022 ➔ Mar 2025 | Trial primary completion date: Aug 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Metabolic Disorders

EMBOLDEN: A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Shire | Recruiting ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders

EMBOLDEN: A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Shire | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders

EMBOLDEN: A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: Shire

New P2 trial • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=18 | Enrolling by invitation | Sponsor: Shire | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=18 | Enrolling by invitation | Sponsor: Shire

New P1/2 trial • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=24 | Enrolling by invitation | Sponsor: Shire | Trial completion date: Oct 2023 ➔ Apr 2023 | Trial primary completion date: Oct 2023 ➔ Apr 2023

Trial completion date • Trial primary completion date • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=24 | Enrolling by invitation | Sponsor: Shire | N=18 ➔ 24 | Trial primary completion date: Feb 2018 ➔ Oct 2021

Enrollment change • Trial primary completion date • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=23 | Active, not recruiting | Sponsor: Shire | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=18 | Enrolling by invitation | Sponsor: Shire | Trial primary completion date: Jan 2020 ➔ Feb 2018

Trial primary completion date • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Shire | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Shire | Trial completion date: Apr 2023 ➔ Dec 2024 | Trial primary completion date: Apr 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Metabolic Disorders

HGT-MLD-071: An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Shire | Trial completion date: Sep 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Metabolic Disorders

Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study. (PubMed, Ann Clin Transl Neurol) - P1, P1/2, P2 | "IV rhASA was generally well tolerated. There was no evidence of efficacy in preventing motor and cognitive deterioration, suggesting that IV rhASA may not cross the blood-brain barrier in therapeutic quantities. The relative stability of peripheral nerve function during the study indicates that rhASA may be beneficial if delivered to the appropriate target site and supports the development of rhASA for intrathecal administration in MLD."

Journal • P1/2 data • Cognitive Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Safety of intrathecal delivery of recombinant human arylsulfatase A in children with metachromatic leukodystrophy: Results from a phase 1/2 clinical trial. (PubMed, Mol Genet Metab) - P1/2 | "Intrathecal rhASA was generally well tolerated at doses up to 100 mg EOW. These preliminary data support further development of rhASA as a therapy for patients with MLD."

Clinical • Journal • P1/2 data • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Pharmacokinetic Modeling of Intrathecally Administered Recombinant Human Arylsulfatase A (TAK-611) in Children with Metachromatic Leukodystrophy (MLD). (PubMed, Clin Pharmacol Ther) - "Estimated parameters suggested rapid distribution of TAK-611 from CSF into the putative brain tissue compartment, with persistence in the brain between doses (median distributive and terminal half-lives in the CNS: 1.02 and 477 hours, respectively). This model provides a valuable basis for understanding the pharmacokinetic distribution of TAK-611, and for pharmacokinetic/pharmacodynamic analyses of functional outcomes."

Clinical • Journal • PK/PD data

Research study to determine the effects of an investigational drug, SHP611 on patients with with Late Infantile Metachromatic Leukodystrophy (MLD) specially the gross motor function, using the Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with matched historical control data in children with MLD. (clinicaltrialsregister.eu) - P2; N=35; Sponsor: Shire Human Genetic Therapies, Inc.

Clinical • New P2 trial