Apabetalone (RVX-208) for Fabry disease

Last updated April 10, 2024, by Lindsey Shapiro, PhD
Fact-checked by Ana de Barros, PhD

What is apabetalone for Fabry disease?

Apabetalone (RVX-208) is an oral therapy that was being developed for the treatment of Fabry disease as an add on to enzyme replacement therapy (ERT), but clinical testing in Fabry patients has been withdrawn due to changes in the priorities of its developer, Resverlogix.

The company still is investigating apabetalone as a possible treatment for other disorders, including post-COVID-19 conditions, cardiovascular disease, chronic kidney disease, vascular dementia, and pulmonary arterial hypertension.

Therapy snapshot

How does apabetalone work?

In Fabry disease, a fatty molecule called globotriaosylceramide (Gb3) toxically accumulates in cells due to a lack of the alpha-galactosidase A enzyme that’s needed to break it down. This buildup is damaging to organs, including the kidneys and heart. Gb3 accumulation also activates the immune system, leading to pro-inflammatory responses that contribute to organ damage and disease progression.

Apabetalone is a selective inhibitor of the BET (bromodomain and extra terminal) family of proteins. BETs regulate the activity of a wide range of genes, activating those involved in the immune system and inflammation when a person gets sick.

BET inhibition by apabetalone has been shown to reduce expression of inflammatory markers in various disease models, and preclinical studies showed that the medication inhibited inflammatory processes in immune cells from Fabry disease patients being treated with ERT. By blocking this inflammation, it was expected to slow the progression of organ damage in people with Fabry disease.

How was apabetalone administered?

In clinical trials involving Fabry patients, apabetalone was to be administered orally at a dose of 100 mg, taken twice daily (12 hours apart).

Apabetalone in clinical trials

An open-label Phase 1/2 clinical trial (NCT03228940) was designed to evaluate apabetalone’s safety and effects on disease biomarkers among adults with Fabry disease, ages 18-75. The trial, which was set to open in 2022, was withdrawn that same year due to a change in Resverlogix’s developmental priorities.

Common side effects of apabetalone

No clinical trials of apabetalone were completed in Fabry disease patients, and its side effect profile in this population is not known.

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