# 2025 FDA TIDES (Peptides and Oligonucleotides) Harvest

## TL;DR

In 2025, the FDA approved new peptide and oligonucleotide drugs, highlighting advances in treating rare diseases like antithrombin deficiency and Barth syndrome.

## Contribution

This paper reviews the 2025 FDA approvals of novel TIDES, emphasizing their structures, mechanisms, and clinical significance.

## Key findings

- Three new oligonucleotide drugs were approved in 2025 for rare diseases.
- Elamipretide became the first treatment for Barth syndrome.
- GalNAc-mediated delivery is a key platform for liver-targeted oligonucleotide therapies.

## Abstract

In 2025, the FDA approved 46 novel drugs, including four TIDEs (one peptide, three oligonucleotides, and one antibody drug conjugate containing peptide as a payload). The three approved oligonucleotide therapeutics—fitusiran, donidalorsen, and plozasiran—bring the total number of approved oligonucleotide drugs to 24 across 16 clinical indications since 1998. Fitusiran and donidalorsen are the first oligonucleotide therapies approved for antithrombin deficiency and hereditary angioedema, respectively, while plozasiran represents the second approved therapy for familial chylomicronemia syndrome. All three agents employ GalNAc-mediated hepatocyte targeting, highlighting the continued importance of liver-directed delivery platforms in oligonucleotide drug development and underscoring the growing clinical maturity of this therapeutic class. Peptide-based therapeutics continue to emerge as pioneering treatments for longstanding diseases. In 2025, elamipretide further expanded this paradigm by becoming the first disease-specific treatment approved for Barth syndrome. This review provides an overview of TIDES approved in 2025, with emphasis on their chemical structures, medical targets, modes of action, routes of administration, and associated adverse effects.