resamirigene bilparvovec (AT132) / Astellas - LARVOL DELTA

Long‑Term Safety and Efficacy of an AAV‑Based Gene Therapy forX‑Linked Myotubular Myopathy (ICNMD 2026) - P2/3 | "With up to 7.25 years of follow-up, most children with XLMTM who received resamirigene bilparvovec continued to show improvements in respiration and motor function. Since the primary analysis, 4 additional participants began walking independently and 1 achieved independent sitting. During long-term follow-up, no further deaths were reported, and resamirigene bilparvovec demonstrated a favorable safety profile."

Clinical • Gene therapy • Cardiovascular • Gene Therapies • Hepatology • Inflammation • Liver Failure • Myositis

Gene therapy for children with X-linked myotubular myopathy: a plain language summary of publication for the ASPIRO study. (PubMed, Ther Adv Rare Dis) - "This summary describes the results of a research study (clinical trial) called ASPIRO that was published in the Lancet Neurology in 2023. This study looked at an investigational gene therapy called resamirigene bilparvovec (also known as AT132) as a possible treatment for children with a disease called X-linked myotubular myopathy (abbreviated as XLMTM)."

Journal • Review • Gene Therapies • Myositis

An algorithm for discontinuing mechanical ventilation in boys with x-linked myotubular myopathy after positive response to gene therapy: the ASPIRO experience. (PubMed, Respir Res) - P2/3 | "In the ASPIRO clinical trial (NCT03199469), participants receiving a single intravenous dose of an investigational gene therapy (resamirigene bilparvovec) started showing significant improvements in daily hours of ventilation support compared with controls by 24 weeks post-dosing, and 16 of 24 dosed participants achieved ventilator independence between 14 and 97 weeks after dosing...A group of experts in respiratory care and physiology and management of children with XLMTM developed an algorithm to safely wean children in the ASPIRO trial off mechanical ventilation as their respiratory muscle strength increased. The algorithm developed for this trial provides recommendations for assessing weaning readiness, a stepwise approach to weaning, and monitoring of children during and after the weaning process."

Gene therapy • Journal • CNS Disorders • Gene Therapies • Myositis • Respiratory Diseases

Ten-Year Durability of AAV8-MTM1 Gene Transfer in a Canine Model of X-Linked Myotubular Myopathy (ASGCT 2024) - "Here we present new data showing that a one-time treatment for a muscle disease can last more than a decade without any loss of effectiveness. These data will answer key questions like what proportion of muscle nuclei need to be targeted by AAV for long-term therapeutic effect and how does protein expression remain stable over years."

Preclinical • CNS Disorders • Fibrosis • Gene Therapies • Hepatology • Liver Failure • Myositis • Respiratory Diseases

Longitudinal changes of Anti-AAV9 and Anti-AAVrh74 antibodies in treated and untreated patients (MDA 2024) - "Subjects received SGT-001 (N=7), Zolgensma (N=7), PF-06939926 (N=2), AT132 (N=1), LYS-SAF302 (N=1), PGTC PD-AAV004 (N=2), all AAV9 products... 169 untreated subjects (115 male) with 1 plasma/serum sample for analysis were included. Median age was 13 (3-37). Of these, 92 (54%) were seropositive for Anti-AAV9 IgG at initial collection."

Clinical • CNS Disorders • Gene Therapies • Immunology

Rapid Transition of AT132 to Clinical Testing by an Industry Sponsor (MDA 2024) - No abstract available

Clinical

ASPIRO: Gene Transfer Clinical Study in X-Linked Myotubular Myopathy (clinicaltrials.gov) - P2/3 | N=26 | Active, not recruiting | Sponsor: Astellas Gene Therapies | Phase classification: P1/2 ➔ P2/3 | Trial completion date: Oct 2030 ➔ Mar 2030

Gene therapy • Phase classification • Trial completion date • Gene Therapies • Myositis

Effects of gene replacement therapy with resamirigene bilparvovec (AT132) on skeletal muscle pathology in X-linked myotubular myopathy: results from a substudy of the ASPIRO open-label clinical trial. (PubMed, EBioMedicine) - P1/2 | "Muscle biopsies from individuals with XLMTM treated with resamirigene bilparvovec display statistically significant improvement in organelle localisation and myofibre size during a period of substantial improvements in muscle strength and respiratory function. This study identifies valuable histological endpoints for tracking treatment-related gains with resamirigene bilparvovec, as well as endpoints that did not show strong correlation with clinical improvement in this human study."

Journal • Gene Therapies • Myositis • Respiratory Diseases

Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial. (PubMed, Lancet Neurol) - P=N/A, P1/2 | "Most children with X-linked myotubular myopathy who received MTM1 gene replacement therapy had important improvements in ventilator dependence and motor function, with more than half of dosed participants achieving ventilator independence and some attaining the ability to walk independently. Investigations into the risk for underlying hepatobiliary disease in X-linked myotubular myopathy, and the need for monitoring of liver function before gene replacement therapy, are ongoing."

Journal • Gastrointestinal Disorder • Gene Therapies • Hepatology • Infectious Disease • Liver Failure • Myositis • Pneumonia • Respiratory Diseases • Septic Shock

High-throughput transcriptome analyses from ASPIRO, a phase 1/2/3 study of gene replacement therapy for X-linked myotubular myopathy. (PubMed, Am J Hum Genet) - "We aimed to characterize the transcriptomic changes in muscle biopsies of individuals with XLMTM who received resamirigene bilparvovec (AT132; rAAV8-Des-hMTM1) in the ASPIRO clinical trial and to identify potential biomarkers that correlate with therapeutic outcome...Finally, the machine learning model identified five genes, including MTM1, as potential RNA biomarkers to monitor the progress of AAV gene replacement therapy. These findings further extend our understanding of AAV-mediated gene therapy in individuals with XLMTM at the transcriptomic level."

Journal • P1/2 data • CNS Disorders • Gene Therapies • Inflammation • Metabolic Disorders • Myositis • Respiratory Diseases

Long term outcomes for X-Linked myotubular Myopathy (XLMTM) with gene replacement therapy, resamirigene bilparvovec: Preliminary results from ASPIRO (WMS 2022) - P1/2 | "Overall, significant improvements and maintenance of ventilator independence, respiratory muscle strength and skeletal muscle function were observed compared to untreated controls. These substantial long-term durable improvements must be weighed against the occurrences of fatal serious adverse events, for which the ASPIRO program is on clinical hold while relevant clinical information is being gathered and reviewed."

Hepatology • Myositis