Today 17th December 2024, Astellas Pharmaceuticals shared an update about:-

    • The status of the XLMTM gene therapy programme at Astellas
    • The EXCEL liver natural study
    • The XLMTM Patient Insights Panel

Please read their letter below or download it here: FINAL_XLMTM Community Letter – December 2024 (PDF)

“Dear XLMTM Patient Community,

We are reaching out to share an update on the XLMTM development program, which we recognize and appreciate you have asked for, to keep you informed about where we are with the program.

AT132 XLMTM Program Status

In January 2020, Astellas bought Audentes Therapeutics. At that time, Audentes Therapeutics was carrying out an early-stage research study (clinical trial) to learn whether its investigational gene therapy (called AT132) could be used to treat XLMTM. This clinical trial was called the ASPIRO study. Sadly, four boys passed away whilst they were part of the clinical trial and investigational research with AT132 was suspended (put on clinical hold) due to safety concerns.

The AT132 program is still on clinical hold, and Astellas is in ongoing discussions with the Food and Drug Administration (FDA) in the USA and health authorities outside of the USA about next steps. Because of this, we will not invite new patients to take part in the ASPIRO study. We have been carrying out laboratory investigations on AT132 since the ASPIRO study was put on hold, to better understand AT132 and its effects. If AT132 were to be used for research in humans at any time in the future, this would be carried out in a new clinical trial that would need to be reviewed by the FDA and other health authorities outside of the USA.

Children who were already dosed with AT132 in the ASPIRO study will continue to be monitored for a period of ten years from when they received the gene therapy. We still need to collect important long-term data from ASPIRO to help us understand the long-term impact for boys treated with AT132.

KT430 XLMTM Program Status

In June 2023, Astellas announced an Exclusive Licensing Agreement with Kate Therapeutics. This agreement gives Astellas the rights to develop, manufacture, and sell an investigational gene therapy called KT430. Since then, we have been focusing on carrying out further laboratory research on KT430 and setting up the manufacturing process. Astellas is now waiting for the laboratory research safety data that are needed to file an Investigational New Drug (IND) application. The IND is a request to the FDA to use an investigational product in people. We hope to file an IND for KT430 next year.KT430 has recently received the following designations from the FDA:

      • Rare Paediatric Disease designation, awarded on 19 September 2024. The FDA awards this status when a product is intended to treat or prevent a rare disease that primarily affects children (people under 18 years of age).
      • Orphan Drug designation, awarded on 22 October 2024. The FDA awards this status to products that treat rare diseases or conditions.

    We welcome these designations which help support the development of potential innovative treatments for people living with rare diseases.

    As we look to the future of the XLMTM program, we know that safety is a top priority for the XLMTM community. We want to reassure you that it is ours, too.

    Understanding of Serious Adverse Events (SAEs) in ASPIRO

    The ASPIRO study highlighted gaps in knowledge about the impact of XLMTM on the liver. To help us better understand this, Astellas is starting an observational study called the Epidemiological Study of XLMTM and Clinical Expression in the Liver (EXCEL). This study will last for one year and aims to enroll approximately 50 male participants under 18 years of age, from Canada, the UK, and the USA. People taking part in this study will receive standard of care treatment based on their physician’s discretion, and there will be no investigational treatments involved. Home health nursing services will be implemented to facilitate taking part in the study from home.

    We would like to thank the XLMTM community representatives, as well as the experts in disease genetics and hepatology, for their valuable input in shaping this study as part of the EXCEL study Steering Committee.

    Working with the XLMTM Community

    At Astellas we are committed to including the patient voice at every stage of the medicines’ development lifecycle, through bringing patient organisation representative insights into the design and implementation of our studies. This helps us to make sure that the medicines we develop reflect what truly matters to those who are living with, or impacted by, a disease.

    We are pleased to be working with a panel of patient organisations (an XLMTM Patient Insights Panel*) from Europe, Latin America, and the USA to seek their input and insights throughout the research and development process. We look forward to continuing to work with the Patient Insights Panel as we move forward.

    Looking to the Future

    We acknowledge that the process of potentially starting a new investigational trial may bring about mixed feelings in the community. These thoughts and feelings are important to us, and it is Astellas’ priority to continue to keep open lines of communication and to work together to address any concerns you may have as we move forward.

    We want to assure you that the lessons that we’ve learned from the ASPIRO trial will always be with us. We are committed to honoring the legacy of the four boys you lost and to ensuring that their contributions help guide us in our efforts as we continue with the program.

    Thank you for being a vital part of this process. We look forward to strengthening our relationships and working collaboratively with you as we navigate this next stage in the hope of achieving better outcomes for people living with XLMTM and their families.

    With very best wishes,
    Lucy James and Chelsea Moran

    *The EXCEL Steering Committee and the XLMTM Patient Insights Panel have been organised and funded by Astellas. Members have been offered payment for their time and expertise.
    This communication includes information about Astellas investigational compounds that have not yet been approved by regulatory agencies for specific indications. Information about current usage statistics and/or about other potential future uses is intended only for discussion of the investigational compound’s regulatory lifecycle development and should not be interpreted as an intent to promote unapproved uses. The contents of this communication should not be used in any manner to directly or indirectly promote or sell the investigational product for unapproved uses. Astellas prohibits the promotion of unapproved uses and complies with all applicable laws, regulations, and company policies.”