Rescue of an orphan drug points to a new model for therapies for rare diseases

Telethon Foundation has decided to take over the licence to produce and distribute Strimvelis, a gene therapy product that is the only available cure for a rare condition called ADA-SCID, and that the biopharma company Orchard Therapeutics had discontinued in 2022. It’s the first time in the world that a non-profit organisation takes on such a role.

ADA-SCID is a very rare congenital condition that severely compromises immune defence, it is caused by a defect in a gene that encodes for the enzyme adenosine deaminase and affects about 15 newborns per year across Europe. In the 2000s scientists of the San Raffaele-Telethon Institute for Gene Therapy in Milan, funded by Telethon Foundation, developed a one-shot treatment that removes the cause of the disease. Bone marrow stem cells collected from patients are enriched with correct copies of the faulty gene, delivered by genetically modified viruses. Then the newly functioning cells are infused back to the patients.

In 2016 the European Medicines Agency (EMA) approved the product, called Strimvelis, and the manufacturing and marketing rights eventually went to Orchard, which distributed it until 2022, when it concluded that it was not economically viable.

In recent years several gene therapy or stem cell products have been dropped by commercial manufacturers, cutting off access to life-saving treatments. Shortly after Strimvelis was discontinued in 2022, the Modena-based company Holostem, which introduced the first stem-cell based therapy approved in Europe, also announced it was ceasing activity because its main industry funder had withdrawn.

Production costs for treatments that require complex cell manipulation and clinical grade material, like viral vectors, are extremely high. “When the product addresses an ultra-rare disease, the number of eligible patients is too small to balance the costs and provide profit,” says Armando Genazzani, professor in pharmacology at the Università del Piemonte Orientale, member of the Italian Society of Pharmacology. “To make the business profitable, companies should set a price for each patient that would be excessively high for national health services and the insurance sector”.

Under the new scheme, the enriched cells will still be produced by the AGC Biologics pharmaceutical facility, located on the San Raffaele Campus of the Telethon Institute for Gene Therapy, and that was previously manufacturing them on behalf of Orchard. The treatment will be administered exclusively at the San Raffaele Hospital.

“We established a dedicated scientific service and hired specialized staff to manage pharmacovigilance”, says Francesca Pasinelli, general manager of Telethon Foundation. “It’s a big financial commitment, but we can afford it because we are a non-profit organisation. We just have to balance costs. Our revenues, in addition to donations, come from reimbursements by the National Health Service for Italian and European Union patients, as well as from private funds and insurance for patients outside the European Union.”

In the coming months, the Telethon Foundation is going to apply for EMA’s authorisation to market another gene therapy product dropped by Orchard and originally developed in Milan, a treatment for Wiskott-Aldrich Syndrome, also a rare congenital immunodeficiency. Unlike Strimvelis, this product can be cryopreserved and delivered to clinical centres in other European countries, so Telethon will have to deal with their national authorities to negotiate reimbursements.

“The industry, patients’ associations and no profit organisations are closely watching developments and more charities may follow the path”, says Genazzani. “EU authorities might help by simplifying regulatory processes, granting tax incentives to producers and facilitating cross-border mobility of patients with ultra-rare diseases to access treatments.”

Last year, a group of academics from different European countries founded a consortium called AGORA (Access to Gene therapies fOr RAre disease) committed to overcome national borders and tackle the problem from an international perspective. Claire Booth, professor in gene therapy and paediatric immunology at the Great Ormond Street Hospital in London, co-founder of AGORA, welcomes the initiative of the Telethon Foundation. “It’s a positive step,” she says. “I hope we’ll see more and more hospitals, academic and research organisations exploring options to facilitate access to transformative drugs for patients.”