Applied Clinical Trials
European Union faces a critical view on its pediatric drug development situation, highlighting a lack of treatment, infrastructure, reimbursement, and regulatory agreement.
There are dangers in complacency. It is just over a year ago that the European Union published a self-congratulatory report on its progress in promoting the development of medicines for children. At the time, that move provoked some skeptical response; for instance, “European Union gives itself top marks for its pediatric medicines regulation.” But a year on, a much more critical view of the situation has emerged among European pediatricians, drug developers, and-above all-parents of children with unmet needs. The European Forum for Good Clinical Practice teamed up with the Drug Information Association to mount a two-day review of the state of play in Brussels at the end of October, and their conclusions were far less favorable than the EU’s own assessment of its achievements.
Patient advocates, industry, and physicians spelled out the failings they were conscious of. While cancer remains the biggest killer of children by disease, in the 10 years from 2007, only two new cancer drugs were approved for children, compared to more than 50 for adults, pointed out Chris Copland, a prominent UK patient representative. He added that brentuximab vedotin had been approved for Hodgkin’s lymphoma in adults in 2012; trials for pediatric use were still ongoing in 2016.
Regret tempered patient groups’ satisfaction at access-at last-to a treatment for spinal muscular atrophy, because of the long delay and the still-limited access. The causative gene was identified in 1995, but the first product, Biogen’s Spinraza, was authorized only in 2017, available only in 2018, and then only in a handful of countries for a handful of patients-less than a tenth of the estimated 20,000 patients in Europe.
Only two drugs are approved anywhere in the world for Duchenne muscular dystrophy, and only one in the EU-Translarna. And that is available only subject to strict limitations and tight conditions, as well as significant delays in securing treatment, even in prosperous European countries.
Christina Bucci-Rechtweg, global head of pediatric and maternal health policy at Novartis, presented a formidable list of obstacles to access to new pediatric medicines and indications. Pediatric research infrastructures are not adequate, and research opportunities are missed. The consequences are gaps in pediatric-specific innovation, in treatment alternatives to high cost new pediatric innovations, and in inadequate supply of age-appropriate formulations.
Marie-Yvonne Douste-Blazy of Servier offered some potential solutions from the point of view of a company. An inventory of disease-based unmet pediatric needs could serve as a common basis for strategic decision-making among industry, regulators, epidemiologists, patient groups, and pediatrics networks, she proposed, particularly if it indicated clearly for each need what research was ongoing.
But another of her priorities was to speed access to innovative drugs, reflecting the widely-supported view at the meeting from industry executives and patients that reluctance to reimburse innovations among Europe’s health insurance systems was another hurdle. Other industry executives spoke of “non-prioritization of pediatrics in payment structures.”
The omnipresent issue of money does indeed underlie much of the difficulty, conceded Evert Jan van Lente, director of EU affairs for the German health insurers association, AOK. But he did not consider that payers were the real obstacle, and nor did he see that tinkering with the system by adjusting incentives would be a sufficient solution. “Extending supplementary protection certificates or market exclusivity are just not appropriate mechanisms,” he said. His starting point was that the return on investment from new pediatric medicines will never be able to compete with the return from new adult medicines, and that a more radical approach and a new development model was needed. In his view, pediatric research should be publicly funded.
Menno Aarnout, the director of the international health insurer organization, AIM, also questioned the ability of current arrangements for pricing and reimbursement in Europe to ensure access to pediatric medicines. Agreement was needed on “a fair, maximum, affordable price that allows for sustainable access to pharmaceuticals.” And to attain this, he envisioned more transparency of clinical data, relative effectiveness and prices, as well as closer collaboration on pricing and reimbursement methods and between regulators, health technology assessment agencies, and payers.
Absent regulatory harmonization
The regulatory framework, too, came in for some adverse comment. Industry executives wanted to see it fitting better within the global drug development process, with mechanisms that avoided the currently experienced long deferrals for starting dates for pediatric studies. They also wanted to see a system that offered greater certainty that the agreed pediatric investigation plan can be effectively completed.
Even regulators at the conference commented on continuing deficiencies in the functioning of the framework. It is not just regulators and scientists that do not always converge in their views, said Dirk Mentzer, the chair of the European Medicines Agency’s (EMA) pediatric medicines committee. He also noted that national authorities were not as fast as they might be in embedding the EU’s pediatric regulation firmly into their own regulators’ work. He said a lot still needs to be done to overcome diverse procedures and approaches leading to divergent evaluations and decisions.
Institutionally, the picture at present is that the European Commission is still conducting its gap analysis of the functioning of its orphan drug incentive scheme, which it plans to complete by March 2019, and this will feed into an overall evaluation of its support for orphans and pediatrics due for publication at the end of next year. Uncertainty, therefore, continues to reign.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium