“Children with cancer ‘denied drugs because of EU rules’,” reports the BBC.
This and other headlines in the media are based on a press release issued by the Institute of Cancer Research (ICR), London. The ICR has called for urgent changes in European Union (EU) regulations.
It says pharmaceutical companies are often granted exemptions from carrying out trials of treatments in people under the age of 18. This in turn means that children can’t be offered the latest cancer drugs, the ICR says, because their safety and effectiveness hasn’t been tested.
Under current EU rules, drugs for cancers that only occur in adults can obtain a “class waiver” which means they are exempted from carrying out trials in children. However, the ICR argues that while many adult cancers (such as lung cancer) do not have direct equivalents in children, this doesn’t mean that adult cancer drugs can’t be effective in children’s cancers.
Modern cancer drugs are often designed against specific molecular mechanisms – for example they target cancers with a particular mutation rather than for a particular cancer type – and these mechanisms may be common to different cancers.
For example, mutations in the gene ALK can cause lung cancer in adults (and other cancers).
Mutations in ALK can also cause a cancer called neuroblastoma (cancer of the nerve cells) in children.
The ICR says some potentially important cancer drugs have been given a waiver from testing in children, even though the drugs could be effective against types of children’s cancer.
What are the current EU rules?
The 2007 EU Paediatric Regulation aimed to improve the health of children in Europe without subjecting them to unnecessary trials, or delaying the authorisation of medicinal products for use in adults.
The regulation led to the establishment of the Paediatric Committee which describes the sort of studies manufacturers must do in children, detailed in paediatric investigation plans.
The Committee can grant deferrals of trials in children for some medicines, until the medicine’s effectiveness and safety in adults has been demonstrated. It can also grant waivers for drugs likely to be ineffective or unsafe in children, are intended for conditions that occur in adult populations, or do not represent a significant benefit over existing treatments for children.
Why does the ICR want the regulation changed?
The current regulation means that drugs developed to treat adult cancers can obtain a waiver.
In collaboration with the European Consortium for Innovative Therapies for Children with Cancer, the ICR have analysed data on the impact of current EU regulations.
They found that of 28 cancer drugs approved for adult marketing authorisation in Europe since 2007, 26 have a mechanism of action relevant for childhood cancers. However, 14 have been waived from being tested in under-18s because the specific adult condition for which the drug is developed does not occur in children.
They give the example of drugs approved for treating adult cancers with mutations in the ALK or EGFR genes. Manufacturers have been granted waivers from testing the drugs in children, even though ALK and EGFR mutations have been shown to play a role in some childhood cancers.
The analysis found that the EU’s regulation on rare or “orphan” conditions has also not been effective in getting cancer drugs to children. They state that of the 25 EU approved orphan medicinal products for cancer, none were registered for children in a different cancer type to that in adults.
What does the ICR want changed?
The ICR wants the waivers system to change. Specifically, it wants the European Commission to refuse to grant waivers to pharmaceutical companies exempting them from testing cancer drugs in children on the basis that the adult cancer targeted does not occur in children.
Waivers are appropriate when an adult cancer drug will not work in childhood cancers. However, the ICR states that they are often granted even when evidence shows that a drug for adult cancers has a mechanism of action that could treat childhood cancers too.
Will regulation change?
The European Commission recently held a public consultation on the paediatric investigation plans system and will be considering whether any changes are needed over the next few months.