Gene therapies for rare diseases are under threat. Scientists hope to save them

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Gene therapies for rare diseases are under threat. Scientists hope to save them


Some gene therapies produce good results but founder commercially.Credit: Eric Piermont/AFP via Getty

It was one of gene therapy’s greatest successes — and greatest disappointments.

Strimvelis is a potent treatment for a devastating genetic disorder of the immune system and one of the first gene therapies to be approved in Europe. But in 2022, the company that sold it announced that it could no longer afford to do so: Strimvelis was highly effective at treating disease, but not at turning a profit.

Now it is getting a second chance. The Italian charity Telethon Foundation in Milan has announced that it will produce Strimvelis itself. “We are making a paradigm shift,” said Francesca Pasinelli, general manager of the Telethon Foundation, in a 12 September statement announcing the decision. “We are the first non-profit organization to take on the commercialization of a gene therapy.”

The charity’s unprecedented scheme offers hope to scientists who have spent decades developing gene therapies for rare disorders, only to find that the standard way of getting those treatments to people in need — licensing them to for-profit companies — is unavailable. Other unorthodox ways to keep these efforts going are also being trialled.

“I think we’re going to start seeing creative solutions, and rather different entities marketing drugs,” says P. J. Brooks, a deputy director of the US National Center for Advancing Translational Sciences (NCATS) in Bethesda, Maryland.

Therapies under threat

In the past two years, two gene therapies besides Strimvelis have been withdrawn from the European market for business reasons after earning regulators’ approval. Concern is mounting that other gene therapies for rare diseases will meet a similar fate, as might upcoming treatments that rely on the related technique of genome editing, which makes targeted DNA changes.

“Gene therapy is where a lot of our hope is,” says Barbara Ballard, director of SCID, Angels for Life Foundation, an advocacy group in Lakeland, Florida. “To tell somebody, ‘We have the technology, but we’re not going to save your kid because we can’t make any money on you’? Really?”

Strimvelis treats an immune disorder called ADA-SCID, part of a group of conditions known informally as ‘bubble baby’ disorder. Children with the condition have mutations in a gene called ADA, resulting in insufficient levels of the ADA enzyme. That leaves them vulnerable to frequent infections, which can be fatal.

A bone marrow transplant can cure some cases of the illness, but many children lack a suitable donor. Other existing therapies only partially restore the immune system.

Strimvelis contains cells from a child’s own bone marrow that have been modified to carry a functional copy of ADA. It was initially developed by researchers at the San Raffaele Telethon Institute for Gene Therapy in Milan, which then licensed it to GSK, a pharmaceutical company based in London. In 2016, Strimvelis became the first gene therapy performed on blood-producing stem cells to win approval in Europe.

A ceiling on sales

But Strimvelis’s market is minuscule. Children with ADA-SCID account for fewer than 1 in 200,000 live births in Europe, and gene therapy is reserved for those who cannot find a suitable bone marrow donor. Furthermore, Strimvelis is produced only in Milan and people seeking treatment must be able to travel there to receive it — a journey that not all children with ADA-SCID can make.

In 2018, GSK sold Strimvelis, along with several other treatments for rare diseases, to Orchard Therapeutics, which is based in London. Four years later, Orchard dropped the drug. “I would say that it is a cure for that disease, and I don’t use the word ‘cure’ very often,” says Brooks. “The fact that two companies dropped it — there’s a problem here.”

The Telethon arrangement could be a test case for other gene therapies for rare diseases, says Luigi Naldini, director of the San Raffaele Telethon Institute for Gene Therapy. “It’s a starting point that we hope we will be able to leverage,” he says.

Innovations take root

Strimvelis is not the only ADA-SCID gene therapy to be abandoned by its corporate owner. Orchard has also halted work on a treatment that is similar to Strimvelis but uses a different method to shuttle the ADA gene into a recipient’s cells. In 2021, the company returned the intellectual-property rights for this treatment to the academic investigators who first created it.

One of those researchers, paediatrician Donald Kohn at the University of California, Los Angeles, is continuing trials with money from the California Institute of Regenerative Medicine in South San Francisco, a state agency that funds stem-cell research. He is also in discussions with the US Food and Drug Administration and companies that can produce the components of a gene therapy, searching for a way to lower the costs of producing the treatment and winning regulatory approval.

Other efforts are under way to reduce the cost of developing and producing gene therapies. NCATS is involved in multiple programmes that are exploring ways to standardize gene-therapy production, in the hope of devising streamlined manufacturing and approval processes. “If we succeed in this, we will change the calculus of what constitutes a ‘disease of commercial interest’,” says Brooks.

Billionaires welcome

But he and others also acknowledge the challenges of producing these treatments outside industry. The harsh reality is that few charities have pockets deep enough to market a gene therapy, says Simone Boselli, director of public affairs at EURORDIS-Rare Diseases Europe, a Paris-based non-profit alliance of patient organizations. With Telethon’s announcement, “a new model is actually taking form”, he says. “But we should be mindful: how many other Telethons can we have?” And few non-profits have the necessary technical know-how, says Grace Hampson, associate director at the Office of Health Economics, an independent research charity in London.

For such reasons, Kohn hopes that he can ultimately entice a for-profit company to take on the ADA-SCID gene therapy he is testing now. But if his treatment cannot draw the eye of a biotech suitor, Kohn says, his plan B is to treat as many children as possible before the cash runs out. “I just went to medical school; I’m learning this regulatory and drug-development stuff as we go along,” he says. “If you know any billionaires, send them my way.”



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