ACTUS-101 / Bayer - LARVOL DELTA

Neonatal gene therapy with AAV2/8-LSPhGAA improves hypertrophic cardiomyopathy in the Gaac.1826dupA knock-in murine model. (PubMed, Mol Genet Metab) - "While systemic AAV treatment yields definitive cardiac correction, the partial skeletal muscle response highlights a clear need for optimization. Consequently, the Gaac.1826dupA mouse serves as a high-fidelity platform for evaluating next-generation genomic correction strategies targeting both cardiac and refractory neuromuscular manifestations of PD."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Gene Therapies • Hypertrophic Cardiomyopathy • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: AskBio Inc | Active, not recruiting ➔ Completed

Trial completion • Pompe Disease

AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: AskBio Inc | Phase classification: P1/2 ➔ P1

Phase classification • Pompe Disease

Screening data from 19 patients with late-onset Pompe disease for a phase I clinical trial of AAV8 vector-mediated gene therapy. (PubMed, JIMD Rep) - "We present clinical parameters and AAV antibody titers for 19 individuals with LOPD undergoing screening for a Phase I clinical trial with an AAV serotype 8 vector targeting hepatic transduction (AAV2/8-LSPhGAA)...None of the participants had significantly elevated alanine transaminase, which has been associated with LOPD and could complicate screening for hepatitis related to AAV gene therapy. We review the parameters considered in screening for eligibility for a clinical trial of AAV8 vector-mediated gene therapy."

Gene therapy • Journal • P1 data • Gene Therapies • Hepatology • Inflammation • Myositis • Pompe Disease

AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease (clinicaltrials.gov) - P1/2 | N=7 | Active, not recruiting | Sponsor: Asklepios Biopharmaceutical, Inc. | Recruiting ➔ Active, not recruiting | N=13 ➔ 7 | Trial completion date: Apr 2028 ➔ Mar 2026 | Trial primary completion date: Apr 2025 ➔ Sep 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Pompe Disease

AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease (clinicaltrials.gov) - P1/2 | N=13 | Recruiting | Sponsor: Asklepios Biopharmaceutical, Inc. | Trial completion date: Jun 2023 ➔ Apr 2028 | Trial primary completion date: Dec 2022 ➔ Apr 2025

Trial completion date • Trial primary completion date • Pompe Disease

Minimum Effective Dose to Achieve Biochemical Correction With AAV Vector-Mediated Gene Therapy in Mice With Pompe Disease. (PubMed, Hum Gene Ther) - "These data indicate that AAV2/8-LSPeGFP transduced all hepatocytes when the 2 x 1011 vg/kg dose was administered, which correlated with partial biochemical correction from the equivalent dose of AAV2/8-LSPhGAA. Together these data support the conclusion that substantial transduction of the liver is required to achieve biochemical correction from AAV2/8-LSPhGAA."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Efficacious Androgen Hormone Administration in Combination With AAV Vector-Mediated Gene Therapy in Female Mice With Pompe Disease. (PubMed, Hum Gene Ther) - "This study evaluated the effect of testosterone on gene therapy with an AAV2/8 vector containing a liver-specific promoter to drive expression of GAA (AAV2/8-LSPhGAA) in female GAA-knockout (KO) mice that were implanted with pellets containing testosterone propionate prior to vector administration...The efficacy of androgen hormone treatment in females correlated with increased mannose-6-phosphate receptor in skeletal muscle. These data confirmed the benefits of brief treatment with an androgen hormone in mice with Pompe disease during gene therapy."

Combination therapy • Journal • Preclinical • Cardiomyopathy • Cardiovascular • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

AAV2/8-LSPhGAA in Late-Onset Pompe Disease (clinicaltrials.gov) - P1/2; N=8; Recruiting; Sponsor: Asklepios Biopharmaceutical, Inc.; Trial completion date: Jun 2022 ➔ Jun 2023; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Pompe Disease

AAV2/8-LSPhGAA in Late-Onset Pompe Disease (clinicaltrials.gov) - P1/2; N=8; Recruiting; Sponsor: Asklepios Biopharmaceutical, Inc.; Trial completion date: Mar 2020 ➔ Jun 2022; Trial primary completion date: Dec 2019 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Pompe Disease

Comparisons of Infant and Adult Mice Reveal Age Effects for Liver Depot Gene Therapy in Pompe Disease. (PubMed, Mol Ther Methods Clin Dev) - "AAV2/8-LSPhGAA (3 × 10 vector genomes [vg]/mouse) was administered to infant (2-week-old) or adult (2-month-old) GAA knockout mice...The relative vector dose for infants was approximately 3-fold higher than adults, when normalized to body weight at the time of vector administration. Given these data, the dose requirement to achieve similar efficacy will be higher for the treatment of young patients."

Journal

AAV2/8-LSPhGAA in Late-Onset Pompe Disease (clinicaltrials.gov) - P1/2; N=6; Recruiting; Sponsor: Actus Therapeutics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open