staff

The European Medicines Agency (EMA) has identified two emerging areas with significant potential for the development of innovative therapeutic solutions in its latest Horizon Scanning reports. The first concerns targeted protein degradation (TPD), an approach designed to eliminate proteins involved in disease. The second explores the potential of microgravity environments for the research, development and manufacture of medicinal products.

EMA’s horizon scanning work is designed to help the European regulatory network anticipate scientific and technological developments. By identifying promising innovations at an early stage, regulators can engage sooner with developers, assess whether existing regulatory tools remain appropriate and, where necessary, consider developing new guidance.

Targeting disease-causing proteins for degradation

One of the areas attracting increasing regulatory attention is the selective elimination of proteins associated with disease, particularly damaged or dysfunctional proteins. Unlike conventional pharmacological strategies, which generally aim to inhibit the activity of a protein, TPD approaches make use of the cell’s natural protein degradation mechanisms to remove the target altogether. According to EMA’s report, this strategy could significantly broaden the range of therapeutically accessible targets. In particular, it could offer new ways of addressing proteins traditionally regarded as “undruggable”, including transcription factors, scaffolding proteins and highly homologous targets.

Among the different approaches currently under development, EMA experts identify two technologies as being particularly advanced. Proteolysis-targeting chimeras (PROTACs) have reached the most mature stage, with the first product already approved by the FDA and around 40 additional candidates in development, predominantly in oncology. Another emerging field involves induced-proximity compounds, designed to bring two proteins into close contact inside the cell. This proximity enables one protein to modify, deactivate or promote the elimination of the other. Most candidates based on this mechanism are still at the preclinical stage.

A related class is represented by molecular glue degraders. These small molecules promote or stabilise an interaction between a target protein and an E3 ligase, leading to ubiquitination of the target and ultimately to its degradation. Examples of compounds acting through this type of mechanism include thalidomide, lenalidomide and pomalidomide. Despite their therapeutic potential, TPD medicines present a number of development challenges. These include complex formulation and manufacturing requirements, the possibility of off-target activity, tissue-specific differences in E3 ligase biology and toxicity profiles that may vary between species. Some PROTACs, for instance, incorporate thalidomide-derived components, which require particular attention because of their potential reproductive and developmental toxicity.

EMA also points to the possibility of non-linear exposure-response relationships, an issue that may make careful optimisation of doses and dosing schedules particularly important during clinical development.

Exploring pharmaceutical development in microgravity

The second Horizon Scanning report looks beyond terrestrial laboratories. The International Space Station (ISS) has already provided a unique environment for studying pharmaceutical substances under microgravity, and interest is growing in the potential use of these conditions during specific stages of medicinal product research, testing and manufacturing. EMA’s report highlights, in particular, potential applications in macromolecular crystallisation and structural research. Microgravity can reduce phenomena such as sedimentation and convection, potentially allowing proteins to form crystals with improved characteristics. This could support structural studies and contribute to a better understanding of biologically relevant macromolecules.

Reduced-gravity environments may also offer advantages for three-dimensional cell culture, including the development of spheroids, organoids and tissue-chip systems. Another area of interest concerns stability studies conducted aboard the ISS. In the longer term, this research could contribute to the development of “space pharmacies”, raising new questions about packaging, storage conditions, product degradation and shelf life during extended space missions.

From a regulatory perspective, however, the field remains at an early stage. EMA notes that no dedicated framework currently exists for pharmaceutical development and manufacturing in microgravity. Nevertheless, existing pharmaceutical legislation, including the application of GMP principles throughout the medicinal product lifecycle, together with current innovation-support mechanisms, appears capable of accommodating exploratory projects.

Several issues would still need to be addressed before more advanced applications become possible. These include demonstrating product comparability and adequate process control, establishing suitable approaches for the inspection and supervision of remote or autonomous manufacturing activities, and clarifying the broader regulatory framework.

The involvement of multiple organisations in space-based pharmaceutical activities also raises questions about legal responsibilities, while dependence on highly specialised infrastructure makes continuity of supply another factor requiring careful consideration.

For these reasons, EMA experts currently favour early engagement between developers, regulators and subject-matter experts rather than an immediate focus on marketing authorisation applications. Such dialogue could help regulators build expertise, improve preparedness for future submissions and develop assessment approaches for first-in-class technologies. Only if recurring regulatory gaps emerge as the field develops would the introduction of dedicated new guidelines become necessary.