RNA-targeted agents are drugs based on short single or double stranded nucleic acid molecules (known as antisense oligonucleotides) which are designed to bind specific RNA sequences, ultimately altering the expression of targeted genes. They represent an emerging area in drug development and promising therapies for many rare and ultra rare diseases, since approximately 80% of them are due to a monogenic mutation.

To date, eleven antisense oligonucleotides were authorised by the European Medicine Agency (EMA) for rare diseases. Dawnzera® is the most recently approved one, on 19 January 2026. Notably, it is the first RNA-targeted treatment intended for prophylaxis, indicated for people aged 12 years and older with hereditary angioedema (HAE), a rare chronic disease, characterised by recurrent debilitating attacks of severe swelling (angioedema) in various parts of the body. A Paediatric Investigation Plan (PIP) is ongoing as agreed by the EMA Paediatric Committee (Its active substance, donidalorsen, is an antisense oligonucleotide designed to target the plasma prekallikrein (PKK), a key protein that activates inflammatory mediators central to the disease’s . By reducing plasma prekallikrein production, donidalorsen effectively interrupts the inflammatory .

This novel, RNA-targeted treatment has proven to be a significant advance for people with hereditary angioedema, offering exceptional efficacy coupled with convenient subcutaneous administration and a favourable safety profile. The result is significant for the entire rare disease community, as it offers a preventive strategy instead of just a therapeutic approach, providing a new way to address unmet medical needs and improve patients’ quality of life.

Find out more here: Dawnzera | European Medicines Agency (EMA)