Facilitating the authorization of pediatric and orphan drugs

Ataxia, beta-thalassemia, sickle cell anemia... A rare disease is declared as such when it affects one person in 2,000. This figure may seem low, yet 30 million Europeans are affected by one of them, including 700,000 Belgians. However, the vast majority of these infections are orphan diseases, as there is no suitable treatment, and little research into them. A situation exacerbated by the difficulty of validating new treatments.

"Or, in the case of rare or pediatric diseases, this type of study is very difficult to carry out, because few patients are available, or because these are fragile populations who cannot be asked to follow a heavy protocol. The result is clinical data that are difficult to interpret with standard methods, which can lead to inconsistencies and disparities in decision-making."

To remedy this, in 2024 the European Commission funded the ERAMET project to facilitate the adoption of computer modeling and simulation methods, also known as in silico, for the development and evaluation of orphan and pediatric drugs. Methods in which Flora Musuamba Tshinanu, professor at the Pharmacology and Clinical Toxicology Research Unit, is a specialist: "There are more and more tools available to simulate in silico the action of drugs at the cellular, organ, patient or even population level, and to anticipate responses to treatment", she reveals. "Using data generated for more common diseases or adult populations, it is possible to make predictions about the action of drugs intended for rare or pediatric diseases."

But for the time being, the full potential of this type of approach is yet to be exploited within drug regulatory agencies. "There is as yet no clear protocol for taking into account data obtained in silico," notes the researcher. Our project therefore aims to help agencies by setting up a system of standards."

With a budget of 6 million euros, coordinated by UNamur and also involving four other European universities, but also the regulatory agencies of four countries including Belgium, and SMEs, the ERAMET consortium therefore aims to set up an analysis platform, as well as pilot studies based on a number of pediatric and rare diseases, such as ataxia, and several respiratory and hematological diseases. "The strength of this project is that it integrates both universities and regulatory agencies, so that all together we work to improve the system,"judges the scientist. "Our aim is to integrate new types of in silico analysis routinely into evaluation processes."

As such, the ERAMET project aims to test the credibility of the various methods. "It's not a question of forcing their acceptance at all costs, but of setting up criteria and standards enabling them to be considered as alternatives, and thus understand their value, advantages and disadvantages", Flora Musuamba Tshinanu insists.

A challenge made all the more important by the fact that ERAMET has the particularity of integrating artificial intelligence (AI) into these new tools. "We intend to use AI on two levels,"enumerates the researcher. "Firstly as an additional alternative method, alongside the more pharmacological approaches of modeling and simulation. But AI will also be integrated into a platform dedicated to addressing these issues and developing standards, in order to automate them and thus ensure their sustainability."

"These in silico approaches have the advantage of being able to integrate, in an original way that differs from current practices, in vitro, in vivo and clinical data, but also so-called "real-life" data, adds the scientist. "The latter, derived from patients' medical registers, however, involve a great deal of uncertainty, so integrating them represents a real challenge."

Although ERAMET aims to help regulatory agencies, it will also and above all benefit patients. "At present, the regulatory system is quite compartmentalized, Prof. Flora Musuamba Tshinanu believes. "Each field, from in vitro studies to clinical studies, focuses on what's important to it. And in the end, we sometimes lose sight of the real impact for the patient."

The researcher therefore wants to propose a change in culture. "Rather than evaluating each piece of data separately, we propose observing them in an integrated way, focusing on the issues that are important in regulatory decision-making in favor of the patient, she explains. "This will make it possible, for example, to see whether certain weaknesses in quality data cannot be compensated for by excellent clinical data, and vice versa. In the end, the central question is that of the benefit-risk balance, which must be favorable for the patient, and it is this that must guide all others."