Measures to promote the testing of medicines in paediatric patients have resulted in a significant reduction in the off-label use of adult medicines in children, says the European Commission.
In the 10 years since the Paediatric Regulation came into force, there have been 260 new medicines authorised for use in children, which an EC report says “would have not been achieved without specific legislation and underlines its continued relevance”.
However, there are still areas of weakness in the system. For instance, more effort is needed to ensure an even spread among therapeutic categories rather than areas linked to research priorities in adults rather than children. There is still widespread (and sometimes lengthy) deferrals and waivers of paediatric investigation requirements by drug developers, and there remains a pressing need to improve matters when it comes to rare diseases.
“In diseases that are rare and/or unique to children and which in many cases are equally supported through the orphan legislation, major therapeutic advances often failed to materialise,” says the report. It is implementing a review of the paediatric and orphan drug regulations to see why this is happening, which is due to report in 2019.
The bulk of paediatric investigation plans (PIPs) completed during the period have been in immunology/rheumatology (14%), infectious diseases (14%), cardiovascular diseases and vaccines (10% apiece), says the report, but cancer is trailing with just 7% of the total.
“When we consider the advances in adult oncology, it upsets me deeply that we have not made the same progress in treating the cancers that affect children,” commented Vytenis Andriukaitis, Commissioner for Health and Food Safety. “In the next 10 years we must focus on making similar breakthroughs for children.”
One early finding is that the paediatric use marketing authorisation (PUMA) process – which like the orphan drug regulations is designed to provide 10 years’ market exclusivity in return for testing off-patent medicines – has been a failure with only three granted in the decade.
The reasons behind this are not yet clear, but could stem from drug developer fears that a PUMA will not prevent physicians from continuing to use cheaper products with the same active ingredient or substitution for cheaper products in pharmacies, as well as national healthcare payers’ reluctance to agree premium pricing for PUMA products.
The MEP who was rapporteur for the Paediatric Regulation – Françoise Grossetête – welcomed the report but said it was “long overdue” and reveals some key obstacles holding back paediatric medicines development.
These include “off-label use of products designed for adults, un-adapted rewards for innovation, and the lack of use of the Orphan Drugs Regulation for paediatric indications”, she said.
“I am all the more afraid that the ongoing incentives review carried out by the Commission, together with the current anti-innovation climate, with particularly harsh criticisms against the Orphan Drugs Regulation, would harm children access to medicines in Europe,” concluded Grossetête.
In the short-term, the Commission says it will work with the European Medicines Agency to streamline the current application and implementation of the Paediatric Regulation, for example to ensure speedier completion of PIPs.