Amyotrophic lateral sclerosis Tofersen (marketed as Qalsody) was approved by the FDA for the treatment of
SOD1- associated amyotrophic lateral sclerosis (ALS) in 2023. It was developed by Biogen under a licensing agreement with Ionis Pharmaceuticals. In trials the drug was found to lower levels of an ALS biomarker, neurofilament light change, and in long-term trial extensions to slow disease.
Batten disease Milasen is a novel individualized therapeutic agent that was designed and approved by the FDA for the treatment of
Batten disease. This therapy serves as an example of personalized medicine. In 2019, a report was published detailing the development of milasen, an antisense oligonucleotide drug for
Batten disease, under an expanded-access investigational clinical protocol authorized by the
Food and Drug Administration (FDA).
Cytomegalovirus retinitis Fomivirsen (marketed as Vitravene), was approved by the U.S. FDA in August 1998, as a treatment for
cytomegalovirus retinitis.
Duchenne muscular dystrophy Several
morpholino oligos have been approved to treat specific groups of mutations causing
Duchenne muscular dystrophy. In September 2016,
eteplirsen (ExonDys51) received FDA approval for the treatment of cases that can benefit from skipping exon 51 of the dystrophin transcript. In December 2019,
golodirsen (Vyondys 53) received FDA approval for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript. In August 2020,
viltolarsen (Viltepso) received FDA approval for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript.
Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) Valeriasen is an investigational
antisense oligonucleotide designed to reduce expression of
KCNT1, a gene encoding the sodium-activated
potassium channel KNa1.1 Pathogenic gain-of-function variants in
KCNT1 are associated with
developmental and epileptic encephalopathy, including
epilepsy of infancy with migrating focal seizures (EIMFS), a severe early-life
epilepsy syndrome characterized by treatment-resistant seizures, developmental impairment, and increased childhood mortality. The therapeutic strategy uses an RNase H–activating
RNA-targeted therapy to knock down
KCNT1 transcript levels rather than correcting a specific variant at the
DNA level. In 2026, Nakayama et al reported intrathecal administration of valeriasen in two children with severe
KCNT1 p.Arg474His-associated EIMFS under an investigational clinical protocol. Treatment was associated with reductions in seizure frequency and severity, but ventricular enlargement or
hydrocephalus was observed in both patients, indicating a potential safety concern for some intrathecally delivered knockdown ASOs.
Familial chylomicronaemia syndrome Volanesorsen was approved by the
European Medicines Agency (EMA) for the treatment of
familial chylomicronaemia syndrome in May 2019.
Familial hypercholesterolemia In January 2013
mipomersen (marketed as Kynamro) was approved by the FDA for the treatment of homozygous
familial hypercholesterolemia.
Hereditary transthyretin-mediated amyloidosis Inotersen received FDA approval for the treatment of
hereditary transthyretin-mediated amyloidosis in October 2018. It was developed by Ionis Pharmaceuticals and licensed to
Akcea Therapeutics.
Patisiran (sold under Onpattro) was developed by
Alnylam Pharmaceuticals, and also approved for use in the US and EU in 2018 with orphan drug designation. Its mechanism-of-action is the
active substance of
small interfering RNA (siRNA), which allows it to interfere with and block the production of
transthyretin. As such, it was the first FDA-approved siRNA therapeutic. and soon after, from other regulatory agencies worldwide. == Investigational therapies ==