Etravirine for Friedreich’s ataxia

Last updated Nov. 6, 2023, by José Lopes, PhD
Fact-checked by Patrícia Silva, PhD

Etravirine is an investigational treatment for Friedreich’s ataxia (FA) that aims to increase cell levels of frataxin, the protein whose deficiency leads to damage in multiple bodily systems in FA patients.

Under the brand name Intelence (generic forms are also available), this antiviral medication is approved by the U.S. Food and Drug Administration (FDA) for the treatment of human immunodeficiency virus (HIV) infection.

Fratagene Therapeutics, the company that was developing etravirine for FA, terminated its activities in December 2022.

Therapy snapshot

How does etravirine work in FA?

FA is a rare and progressive neuromuscular disorder caused by mutations in the FXN gene. FXN codes for a protein called frataxin that is key for the functioning of mitochondria, the energy-producing centers of cells. Mutations in FXN lead to frataxin deficiency, mitochondrial dysfunction, and increased levels of toxic reactive oxygen molecules that damage cellular structures through a process known as oxidative stress.

A study using a drug repositioning approach screened 853 FDA-approved medications and found that etravirine could significantly enhance frataxin levels and confer resistance to oxidative stress in cells derived from FA patients. No signs of toxicity were reported.

Further analysis showed no changes in etravirine-induced FXN gene activity, nor in the stability of the messenger RNA (mRNA) molecule that serves as an intermediary between gene and protein. According to the researchers, this suggests improved efficiency in the translation process that converts mRNA to frataxin protein.

Work in a mouse model of FA suggested increased frataxin levels in the heart and skeletal muscle upon treatment with etravirine.

According to the Friedreich’s Ataxia Research Alliance (FARA), which is supporting the advancement of this and other FA treatments, investigations into how etravirine increases frataxin levels could help identify additional therapeutic targets.

How will etravirine be administered in FA?

Etravirine was tested in a Phase 2 clinical trial as oral tablets given over four months. Two daily doses were assessed, 200 mg or 400 mg, given in the morning and evening as 100 mg plus 100 mg or 200 mg plus 200 mg, respectively.

Etravirine in clinical trials

An open-label Phase 2 trial called FAEST1 (NCT04273165) conducted at a site in Italy evaluated the safety and effectiveness of etravirine tablets in 30 FA patients, ages 10 to 40. Participants were randomly assigned to receive a dose of 200 mg or 400 mg of etravirine daily for four months. Treatment was taken at home following a prescription given to the patients.

The primary outcome measure was the number and severity of side effects over the four months. The study also assessed a number of other measures, including: aerobic capacity by measuring peak oxygen uptake while participants were on a stationary bicycle, disease severity, frataxin protein levels in blood cells, heart wall thickness using echocardiography, quality of life, and disability.

According to FARA, recruitment for the trial was completed in August 2022, with 35 participants. Results of the trial have not been disclosed yet.

Common side effects of etravirine

No information has been reported regarding side effects of etravirine in FA patients.

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