Children with cancer in Europe are being denied access to potentially life-saving drugs because a loophole in EU law means that pharma companies can exclude medicines from paediatric clinical trials.
The UK Institute of Cancer Research (ICR) in London and European Consortium for Innovative Therapies for Children with Cancer (ITCC) in France have called for changes to the EU’s 2007 Paediatric Regulation, which allows drugmakers to only test drugs in adults even if there may be some benefit to children.
Out of 28 new cancer drugs approved in the EU for adults since 2007, the ICR estimates that 26 could potentially work in children. However, 14 of these have been exempted from paediatric testing via a waiver system that companies can activate if they argue the specific adult condition for which the drug is developed does not occur in children.
ICR researcher Dr Louis Chesler points out that this position is flawed, as there is often a common mechanism of action between adult and child cancers even if there is no direct equivalent. For example, drugs approved to treat adult cancers with mutations in the ALK or EGFR genes have been granted waivers, even though these mutations play a role in some childhood cancers.
Modern cancer drugs are often designed against specific molecular mechanisms, rather than for a particular cancer types, and many drugs developed for adults “could be effective in children if we were able to test them in clinical trials,” he said.
Ironically, the 2007 Regulation was actually designed to boost testing of drugs in children. Under the legislation companies are obliged to develop a paediatric investigation plan (PIP) describing how a new drug might be tested in children before securing approval unless a waiver is granted.
It also offers drug developers additional patent life if they carry out paediatric trials, but few take up this option, reportedly because of the cost and difficulty in recruiting patients and fears it may delay the approval of a new drug in adults. Drugmakers argue that the waiver system is critical to avoid exposing children to unnecessary clinical trials.
The ICR wants this ‘class waiver’ system scrapped and additional incentives introduced to compensate pharmaceutical companies for the financial challenge of developing drugs for small patient populations.
Meanwhile, the current system for registration of orphan drugs in the EU – which might serve as an alternative route to approval of new childhood cancer drugs – is also failing to deliver the goods.
“Of the 25 EU-approved orphan medicinal products for cancer, none were registered for children in a different cancer type to that in adults,” the ICR points out.
The European Commission started a consultation on the PIP system last October after publishing its first report on the paediatric regulation, which also notes that a “considerable percentage” of clinical trials in PIPs have been deferred to “avoid delays in the authorisation of the corresponding product for adults.”
The ICR says it plans to lobby hard for change on this issue.