Italy’s advanced therapy journey

Advanced Medicinal Therapies (ATMPs), including gene and cell therapies, offer treatment options for patients suffering from rare or ultra-rare diseases. Italy is learning to see expenditure on advanced therapy drugs as an investment but the EU’s pharmaceutical revision is causing concerns among Italian stakeholders.

“We now have 18 advanced therapies in Europe, including 14 gene therapies, two cell therapies, and two tissue therapies,” Celeste Scotti, director of research and development at the Telethon Foundation, told Euractiv.

Of these advanced therapy medicinal products available on the market, 10 have been approved for reimbursement by the Italian Medicines Agency (AIFA), paving the way for wider access for patients. Rare diseases affect at least 2,000,000 people in Italy. Of those, one in five is under the age of 18.

“In Italy, the cost of the drug is covered by the national health system,” said Scotti. His non-profit organisation runs some of the centres of excellence in the field of gene therapies: the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), based in Milan, and the Telethon Institute of Genetics and Medicine (TIGEM), based in Pozzuoli.

For example, cutting-edge gene therapy for the treatment of ADA-SCID, a rare immunodeficiency of genetic origin, which was developed by researchers at the SR-Tiget, is fully reimbursed by the national health system.

Regardless of being a pioneer and one of the leaders in ATMPs – out of the 18 advanced therapies authorised in the European Union, four are the result of Italian academic research – Italy, like other countries, encounters obstacles from the pre-clinical and clinical phases to access and sustainability.

The complexity of ensuring access to treatment

“Talking about accessibility and equitable distribution of drug treatments means dealing with a very wide world, which brings with it a number of facets that each need specific in-depth studies,” the president of UNIAMO – Italian Federation of Rare Diseases Annalisa Scopinaro told Euractiv.

But out of this “very wide world” Scopinaro highlighted economic sustainability, “which must be combined with universal access to advanced and innovative therapies so as not to leave anyone behind”.

In this regard, Scopinaro said that in 2023, UNIAMO, Italy’s association for rare diseases, carried out an institutional training hosted by the Parliamentary Intergroup for Sustainable Innovation in Healthcare to raise awareness in the Italian Parliament of the need for adequate regulatory and legal framework for innovative therapies. 

One of the results of the training course is a document, currently being finalised by the participants, that accepts the proposal of Senators Franco Zaffini and Daniele Manca to introduce in the new Italian budget law an amendment for a fund for gene therapies of approximately 150 million euros.

The discussion of the 2024 budget law is underway in Parliament, which will have to approve and possibly modify it with amendments by 31 December.

A philanthropic business model

In the meantime, Scotti has another proposal: “We need a new model for the development of therapies for rare and ultra-rare genetic diseases and a new model for market access.”

He believes the non-profit sector is a way forward “where there is no business case for a for-profit company because of such high costs and the rarity of the disease”. Indeed, with high costs and few patients, “it is very difficult for such a therapy to be profitable in a for-profit context”.

Telethon is an example of this. Research and development costs are covered by donations by Italian citizens and companies, “who expect a benefit for society from us as a return on their investment, not a financial gain as when investing in a for-profit company,” Scotti said calling the model “philanthropic”.

“In this sense, we hope to be trailblazers. So, what we can say at this time, which is peculiar to Italy, is we hope that others will take their cue from Telethon,” Scotti added.

As an example, Scotti referred to the case of the Strimvelis therapy which is used for the treatment of ADA-SCID, developed in the laboratories of SR-Tiget. 

In 2022 the Anglo-American pharmaceutical company Orchard Therapeutics PLC, owner of the Strimvelis therapy, announced its intention to disinvest in the field of primary immunodeficiencies. 

To prevent the therapy from no longer being available, Telethon took over the marketing task from Orchard, following the positive opinion of the European Medicines Agency (EMA) and the authorisation by the European Commission. 

The Strimvelis therapy drug was authorised in 2016 by the AIFA and has already been administered at the San Raffaele in Milan, the only authorised centre: over the years, 45 patients from 20 countries have been treated.

“The one thing we could not do was to let an effective therapy, developed by Telethon researchers with Telethon funds, be put in a drawer,” Scotti pointed out.

Concern about a potential crisis for advanced therapies in Europe

While Italy is navigating its way in the field, industry players are concerned about the possible exit of pharmaceutical companies from the EU’s market. On April 26, the Commission proposed a new directive and regulation to review and replace the current general pharmaceutical legislation with one of the aims being to make the EU’s market more attractive.

“[The revision] could introduce important changes for access, on the one hand, but on the other hand partly discourage investments in rare diseases and the observation of worrying phenomena,” Scopinaro said. 

The president of UNIAMO stated that “there are already two pharmaceutical companies that have abandoned the European market or even stopped producing the therapy”.

Therefore, it is “necessary to understand the underlying reasons and to try to remedy them, where possible, in order to ensure treatments for those who have no other therapeutic alternatives”.

As a UNIAMO report highlighted, the EMA has a centralised authorisation that refers to the individual states for a definition of price & refund.

This leads to differences in approval times and therefore actual availability for patients in various countries. As underlined by UNIAMO’s president, Italy is suffering some delays in the inclusion of rare diseases in the regional handbooks and is also facing global uncertainty due to the wait for the new EU’s pharmaceutical legislation. 

In the interview, Scotti also raised the alarm regarding the future of advanced therapies in Europe, particularly after Bluebird Bio announced in October 2021 that it would withdraw its Beta Thalassaemia gene therapy from Europe shortly after its approval, due to difficulties in finding a financial settlement.

“Other companies are also at risk of withdrawing their marketing authorisation for commercial reasons,” Scotti noted.

He pointed out that right now the US Food and Drug Administration is approving gene therapies, including others from Bluebird Bio, and “so we are looking at a future where patients in the US will have access to drugs, to effective therapies, that will not be readily available to patients in Europe”.

[Edited by Giedrė Peseckytė/Zoran Radosavljevic]

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