EU warned new medical trial rules will slow approval of vital treatments

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New EU rules threaten to cut the number of new treatments for the rarest diseases because of stricter curbs on medical trials, warn pharmaceutical companies, researchers and patient groups.

Almost 40 groups, including Cancer Patients Europe, the European Association of Urology and World Federation of Hemophilia, have called on Brussels to revise the rules — which give less weight to so-called single-arm trials, where one group of patients do not receive the treatment — before they come into force in January.

They said guidelines issued by EU regulators would make it much harder to get approval for drugs for rare diseases, which only have a handful of patients, by prioritising expensive mass trials. One example is Wiskott-Aldrich syndrome, which causes recurrent infections, bleeding, eczema and an increased risk of developing autoimmune diseases and cancer.

The Alliance for Regenerative Medicine, an advocacy organisation for the cell and gene therapy sector, said randomised control trials, which often require a group of patients to receive a dummy therapy, were too expensive and unethical, as giving an ineffective placebo to a person with such a severe illness would cause unnecessary suffering.

“In rare diseases, single-arm trials are often necessary for ethical, practical and scientific reasons,” said Paolo Morgese, ARM’s Europe vice-president of public affairs.

“The joint clinical assessment guidelines largely ignore this reality and miss a huge opportunity to build a modern EU system. Without changes, the current approach will undermine the EU’s goal to get transformative therapies to patients faster and could prevent access in many EU member states.”

The guidelines were introduced as interest grows in innovative but expensive new cell and gene therapies that treat cancer and rare diseases. According to data provider IQVIA, 76 cell and gene therapies had been launched globally by the end of 2023, double the number a decade earlier.

ARM analysis found that about 80 per cent of approved and available advanced therapies in the EU use single-arm studies that dispense with the control group. By contrast, randomised control trials are considered the most rigorous method of clinical research and involve comparing new treatments with the current standard of care, or a placebo where no standard treatment exists. Researchers often conduct “blind” trials where participants do not know which drug they are receiving.

In an effort to beat the new rules, Fondazione Telethon, an Italian charity, said it was trying to secure authorisation for its experimental treatment for Wiskott-Aldrich syndrome before January.

Stefano Benvenuti, head of public affairs, told the Financial Times that it could not conduct randomised control trials since the condition only affects four in 1mn men. Women who carry the faulty gene are unaffected. A bone-marrow transplant can cure the condition. 

Telethon’s Milan facility is the only location licensed to host the experimental treatment. Benvenuti said he was worried that even if Italy approved it, other countries would not send patients because the guidelines risk “an inconclusive evaluation” for single-arm trials.

Regulators hope the rules, adopted by the European Commission in May, will allow countries to authorise medicines more quickly as countries work together on joint clinical assessments.

“This will help them to decide about its use in the national health system . . . and thus take more effective, timely decisions when bringing medicines to the market,” the commission said at the time.

The new EU guidelines do not rule out single-arm trials and each member state will makes its own decisions based on JCA reports.  

This Regulation on Health Technology Assessment applies to cancer and advanced therapeutics from January 12, and all medicines from 2030. 

Benvenuti said the rules were positive but their implementation guidelines were too restrictive. “The way the guidelines are written right now it is scary,” he said. “In continental Europe we love regulation so much [but] they didn’t consider the peculiarity of some of these advanced therapies.”

He added that many pharma companies had abandoned treatments for rare diseases because it is hard to get a return on investment with so few patients. In 2016 Telethon developed the first treatment for “bubble boy disease”, the autoimmune disease that requires sufferers to live in a sterile environment. 

Its Strimvelis gene therapy, which costs €600,000, has treated 45 patients with adenosine deaminase severe combined immunodeficiency in more than 20 countries.

Additional reporting by Ian Johnston