Donidalorsen: First Approval

Area of Science:

• Pharmacology
• Genetics
• Drug Development

Background:

• Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent swelling attacks.
• Current HAE treatments focus on managing acute attacks, with a need for effective prophylactic options.
• Donidalorsen represents a novel therapeutic approach targeting the underlying pathophysiology of HAE.

Purpose of the Study:

• To summarize the key developmental milestones of donidalorsen.
• To highlight the regulatory pathway leading to its first approval for HAE prophylaxis.
• To provide an overview of donidalorsen as a first-in-class RNA-targeted therapy.

Main Methods:

• Review of regulatory submissions and clinical trial data for donidalorsen.
• Analysis of the mechanism of action of RNA-targeted antisense oligonucleotides (ASOs).
• Documentation of the drug development timeline and key decision points.

Main Results:

• Donidalorsen received its first US approval on August 21, 2025, for HAE prophylaxis in patients aged 12 years and older.
• The drug is a first-in-class, RNA-targeted antisense oligonucleotide (ASO).
• Donidalorsen is currently under regulatory review in the EU and in Phase III development globally.

Conclusions:

• Donidalorsen's approval signifies a major breakthrough in HAE management.
• This RNA-targeted ASO offers a new prophylactic strategy for HAE patients.
• The successful development highlights the potential of ASO technology in treating genetic disorders.