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#apaperaday: Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies

Today’s pick is from American Journal of Medical Genetics by Lekstrom-Himes et al on the opportunity of platform approaches for rare genetic diseases and how the ‘one disease at the time’ approach is not fit for purpose.  DOI: 10.1002/ajmg.c.32031

As mentioned before in these threads: 70% of rare diseases have a genetic cause. Currently there are over 7000 known rare diseases (and counting) affecting over 300 million individuals worldwide. 95% of rare diseases do not have a therapy. Because most rare diseases have a genetic cause, genetic therapies like gene therapy (gene addition), gene targeting therapies (oligonucleotides), and cell therapies offer therapeutic potential. However, the development costs are high for each individual disease.

Authors argue to step away from the one disease at the time approach but shift to a modality platform approach, e.g. siRNA for liver diseases or ASOs that modulate splicing for CNS diseases. I agree – I said something similar during the European Medicines Agency (EMA) meeting on RNA therapy Feb 2.

Note authors discriminate between siRNA, ASO & morpholinos – morpholinos (phosphorodiamidate morpholino oligomers, PMOs) are also ASOs. siRNA & ASOs (PMOs and otherwise) are all oligonucleotide therapies. HOWEVER, each modality (including chemistry) should have its own platform.

Authors stress that for platform development approaches data sharing will be crucial. I agree completely! Which is also why I signed the N1 Collaborative data sharing petition.

Another important thing for developing platform therapy approaches for groups of rare diseases is early diagnosis. Newborn screening is currently very well regulated and it takes years to add diseases – which is too long with the speed at which genetic therapies are developed now.

Authors give recommendations for genetic newborn screening for rare diseases, which includes not only sequencing, but also data analysis, interpretation, genetic counseling and equitable support and follow up for everyone. This will require education as the consequences of genetic newborn screening (potential for gene therapy, cell therapy, oligonucleotide therapy) differ from current newborn screening efforts (dietary changes). Explaining this to parents will be more challenging.

Authors also highlight multiple platform networks already in place, including N1 Collaborative n-lorem foundation for oligonucleotides and the bespoke platform for gene therapy. They also outline that for these types of approaches, new clinical trial/evaluation methods are needed.

This is also part of the networks mentioned, and also of the AGORA network for inherited metabolism and immunity diseases that I highlighted last week. Finally authors outline that the FDA and EMA are interested in facilitating treatment developments for very rare diseases.

Both provide tools such as fast track (FDA) and PRIME (EMA). There is much more in the paper, I just highlighted what struck me as important. Final highlight: we can only do this if we do it together in a multistakeholder approach where we share and communicate.