Astellas Announces Data from ASPIRO Study in X-linked Myotubular Myopathy Published in The Lancet Neurology
Preliminary data analysis on ventilator dependence and motor improvement are reported alongside overall safety findings
TOKYO, Nov. 15, 2023 /PRNewswire/ -- Astellas Pharma US, Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that The Lancet Neurology published a preliminary data analysis from the ASPIRO trial, evaluating the safety and efficacy of investigational AT132 (resamirigene bilparvovec), an adeno-associated viral vector (AAV) gene replacement therapy designed to deliver a functional human MTM1 gene for the treatment of pediatric patients with X-linked myotubular myopathy (XLMTM). The AT132 IND and ASPIRO trial are currently on clinical hold. The manuscript was first published online on November 15th and will be available in the December 2023 print issue of The Lancet Neurology.
Perry B. Shieh, M.D., Ph.D., Professor of Neurology and Pediatrics, University of California Los Angeles, and Principal Investigator for ASPIRO
"There is a real need for treatments for these patients. These preliminary data document for the first time that there is potential for gene therapy to provide clinical improvements in patients with XLMTM, including improvement in ventilator dependence and achievement of major motor milestones. Additionally, important issues related to liver health in participants with XLMTM receiving gene therapy have been identified and will continue to require careful evaluation."
Richard Wilson, Senior Vice President, Primary Focus Lead, Genetic Regulation, Astellas
"We are grateful for the opportunity to share this important analysis. We are focused on patients and the potential impact of gene therapy and are driven to deliver transformational benefits for people living with rare genetic diseases. While we continue our efforts to address the ongoing clinical hold for ASPIRO, this publication serves to provide information that may guide efforts aimed at advancing promising therapies for XLMTM."
The manuscript reports data as of February 28, 2022. At the time of this data cut, the study included 24 boys with XLMTM dosed with AT132. An exploratory analysis was conducted of two dosing cohorts (lower-dose at 1.3 x 1014 vg/kg and higher-dose at 3.5 x 1014 vg/kg) who received a single infusion of AT132, compared with a control group comprised of two subjects who were enrolled but not dosed and 12 children from a natural history study.
At baseline, all participants were ventilator dependent, three were able to sit independently for 30 seconds, and none had achieved more advanced milestones. By 24 weeks post-dosing, the lower-dose cohort demonstrated an estimated 77.7% (95% CI: 40.22, 115.24) greater reduction in mean hours of ventilator support from baseline compared with controls (p=0.0002). The higher-dose cohort demonstrated an estimated 22.8% (95% CI 6.15, 39.37) greater reduction from baseline compared with controls (p=0.0077). Of the 24 boys dosed in the study, 16 participants, including six at the lower-dose and 10 at the higher-dose, achieved ventilator independence as of the data cut. Five participants at the lower-dose and three participants in the higher-dose cohort were able to walk independently; several other major motor milestones were achieved after gene therapy.
There were three deaths in the higher-dose cohort (18%), followed by one death in the lower-dose cohort (14%). All four participants had ongoing hepatic and hepatobiliary serious adverse events (SAEs), which had progressed to cholestatic liver failure at the time of death. Treatment-emergent SAEs were observed in two of the seven participants at the lower-dose, and nine of 17 at the higher-dose. Five of the 20 surviving dosed participants had hepatobiliary SAEs.
Of the 14 participants in the non-treated cohort (two in the control group and 12 from a natural history study), none achieved ventilator independence while five were able to sit unassisted for 30 seconds by the end of the 48-week period. No other motor milestones were achieved.
These data demonstrate the potential of a therapeutic approach for myotubularin replacement using recombinant AAV gene therapy.
About X-linked Myotubular Myopathy
XLMTM places a substantial burden of care on patients, families and the healthcare system, including high rates of healthcare utilization, hospitalization and surgical intervention. More than 80 percent of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support. In most patients, normal developmental motor milestones are delayed or never achieved. Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.
About AT132 for the treatment of X-linked Myotubular Myopathy
AT132 has been granted Regenerative Medicine and Advanced Therapy (RMAT), Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the U.S. Food and Drug Administration (FDA), and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency (EMA).
About Astellas Gene Therapies
Astellas Cautionary Notes
View original content to download multimedia:https://www.prnewswire.com/news-releases/astellas-announces-data-from-aspiro-study-in-x-linked-myotubular-myopathy-published-in-the-lancet-neurology-301989715.html
SOURCE ASTELLAS PHARMA INC.
Company Codes: Tokyo:4503, OTC-PINK:ALPMY