The first ncRNA therapeutic drug approved by food and drug administration (FDA) (1998) and the European medicine agency (EMA) (1999) is called Fomivirsen or Vitravene. The target organ is the eye and works against the cytomegalovirus (CMV) retinitis in immunocompromised patients. The drug functions as an antisense oligonucleotide and binds to the complementary sequence of the mRNA that inhibits the replication of human cytomegalovirus. This therapy can also be categorized as Antisense oligonucleotide (ASO) therapy.
There have been many ASO RNA therapeutics that have been approved by FDA and/or EMA over the years, but it wasn’t until 2018 that the EMA approved the drug called Patisiran/Onpattro. The drug uses ds-siRNA as a mechanism of action and is deemed effective against hereditary transthyretin amyloidosis. The mechanism specifically targets the Transthyretin (TTR) mRNA.
RNA therapeutic targets are not limited to mature mRNA but have been used to target mRNA at different stages of maturation. One such example is Nusinersen (Spinaraza), it functions as an ASO and targets pre-mRNA before splicing that corresponds to Survival of motor neuron 2 gene (SMN 2). This drug therapy was approved by FDA and EMA in 2016 and 2017 respectively.
There are some drugs that have been approved by FDA and not by EMA. This can be seen in the case of an ASO type therapeutics called Eteplirsen (Exondys51) which has been approved by FDA in 2016 but not by EMA. It targets pre-mRNA corresponding to Dystrophin (DMD) and works against Duchenne muscular dystrophy.
There are many additional therapeutics that have been developed and are either in phase I or II of the clinical trials. Current RNA therapeutics in clinical trials range from a variety of target organs and diseases ranging from skin (potential treatment for disease such as keloid) to tumors (squamous cell lung cancer).
To date, for both the FDA and the EMA, ncRNAs are considered as "simple" medical products because of their production by chemical synthesis. When some of them, produced biologically (known as bioengineered ncRNA agents: BERAs), will be put on the market, the status of biological medical products will be applied, which could lead to inconsistencies in the legislation.