The Italian research charity Telethon Foundation is advancing efforts to secure European Union approval for etuvetidigene autotemcel, a gene therapy targeting the rare genetic disorder Wiskott-Aldrich syndrome (WAS). The marketing authorization application (MAA) has been submitted to the European Medicines Agency (EMA) for review.
A 'Rescued' Therapy
Etuvetidigene autotemcel was initially developed by scientists at the San Raffaele-Telethon Institute for Gene Therapy in Milan. Orchard Therapeutics, a biotech firm specializing in gene therapies for rare diseases, previously licensed the therapy but withdrew in 2022 due to strategic and commercial considerations. Telethon Foundation subsequently assumed responsibility for the program.
Mechanism of Action and Clinical Experience
Etuvetidigene autotemcel is designed as a single-administration treatment for WAS patients who do not have a matched family donor for hematopoietic stem cell transplantation, the current standard of care. The therapy involves modifying autologous CD34+ stem and progenitor cells with a lentiviral vector encoding the WAS gene. WAS is a rare disorder affecting platelet production and immune system function, leading to severe infections, bleeding, and autoimmune complications.
To date, 30 patients with WAS have been treated with etuvetidigene autotemcel, including 27 within the clinical development program and three through an early access scheme. Since August 2023, the therapy has been available in Italy for patients over six months old without a matched related donor, under a determination by the Italian Medicines Agency (AIFA).
Expansion to the US
Telethon Foundation's director general, Ilaria Villa, stated that the organization is also working on a submission to the US Food and Drug Administration (FDA) to make the therapy available in the United States.
Telethon's Commitment to Gene Therapy
This marks the second instance where Telethon has taken over the development of a gene therapy after a commercial partner's withdrawal. The first was simoladagene autotemcel, a therapy for adenosine deaminase severe combined immunodeficiency (ADA-SCID). Like etuvetidigene autotemcel, simoladagene autotemcel originated from the San Raffaele-Telethon Institute in Milan and was previously partnered with Orchard Therapeutics.
Telethon Foundation claims to be the first charity worldwide to assume responsibility for the production and distribution of a drug. The organization highlights funding as a key challenge in gene therapy development. Venture capitalists and private investors are often hesitant to support these therapies beyond early-stage clinical trials due to small patient populations and uncertain commercial returns. While grants can fund initial research, they rarely cover the full development and approval process, which requires substantial investment.
High manufacturing costs also pose a barrier. Gene therapy production requires advanced technology, stringent quality controls, and specialized facilities, making scaling expensive. If a gene therapy is deemed commercially unviable, its development may be paused or abandoned.
Addressing Development Challenges
In 2022, the EMA launched a pilot program to support academic and non-profit developers of advanced therapy medicinal products (ATMPs). This initiative aims to help non-profit organizations navigate existing regulatory pathways through fee reductions and waivers for scientific advice, MAA submissions, and pre-authorization inspections. The EMA anticipates publishing initial results from the pilot program this year, outlining key findings and potential areas for regulatory improvement.
