EMA, FDA to facilitate clinical investigation of new medicines for Gaucher disease in children

The document is released for public consultation until 31 August 2014.

The aim of the proposal is not only to facilitate a rapid and smooth agreement of an EMA Paediatric Investigation Plan and FDA Pediatric Study Plan, but also to address the feasibility of developing multiple medicines for a rare disease in a reduced timeframe and in a limited number of patients.

Gaucher disease is a rare condition characterized by the accumulation of specific chemical substances (glucocerebrosides) in certain cells throughout the body. The severity of the disease is extremely variable with a wide range of symptoms. There is a high unmet medical need for children with neurological symptoms, in particular for new routes of administration that would reduce the treatment burden.

A number of medicines are under development for the treatment of this disease; however, since it is a rare condition, recruitment of children in clinical trials has been shown to be difficult.

To address this issue, the joint proposal discusses two complementary approaches:

the extrapolation of efficacy from adults to children which would include the use of modelling and simulation approaches. The EMA and FDA consider that the primary rationale for extrapolation is to avoid unnecessary studies in children for ethical reasons, to increase efficiency, to reduce the burden on children, and to ensure that resources are allocated to areas where studies are most needed;
the possibility to conduct multi-arm, multi-company clinical trials to determine the safety and efficacy of several new medicines at the same time. This approach would allow reducing the total number of children to be included in trials, compared to separate controlled trials, as the same control arm would serve more than one medicine under evaluation. A proposed design for such trials is included in the document.
"The complementary approach proposed would not only facilitate the investigation of new medicines for rare diseases in children but also optimise the number of patients recruited, thereby reducing the burden on children and families," explains Jordi Llinares Garcia, Head of the EMA’s Product Development Scientific Support Department.

Sponsors who wish to make use of these innovative approaches in their development plan are advised to contact the regulatory authorities to get scientific advice. Sponsors have the possibility to approach the EMA or the FDA separately or to request parallel scientific advice from the two regulatory authorities if they wish.

The joint proposal published today is the result of an extensive consultation process with various groups of stakeholders that started in October 2011. As part of this process, the EMA and the FDA organised a joint workshop in September 2012 to gather views from patients, experts and medicines’ developers to discuss the way forward for the clinical investigation of medicines for the treatment of Gaucher disease in children.