The Food and Drug Administration (FDA) has approved Skyclarys™ (omaveloxolone) for the treatment of Friedreich ataxia in patients 16 years of age and older.
Friedreich ataxia is a rare genetic disease caused by mutations in the FXN gene. This leads to a deficiency of frataxin, which results in mitochondrial iron accumulation and oxidative stress. The disease is typically characterized by a progressive decline in coordination, muscle weakness, and fatigue that commonly results in motor incapacitation.
The exact mechanism of action for omaveloxolone in patients with Friedreich ataxia is unknown. However, omaveloxolone has shown to activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway which is involved in the cellular response to oxidative stress.
The approval was based on data from the 48-week MOXIe trial (ClinicalTrials.gov Identifier: NCT02255435), a 2-part study that evaluated the efficacy and safety of omaveloxolone in patients 16 to 40 years of age with Friedreich ataxia. In Part 2 of the study, patients were randomly assigned to receive omaveloxolone 150mg orally once daily (n=51) or placebo (n=52). The final analysis included 40 omaveloxolone patients and 42 placebo patients.
Findings showed that treatment with omaveloxolone met the prespecified primary analysis achieving statistically significantly lower mFARS scores (modified Friedreich’s Ataxia Rating Scale), or less impairment, among patients without severe pes cavus at week 48 compared with placebo (placebo-adjusted difference, -2.41 [95% CI, -4.32, -0.51]; P =.0138). In a post hoc analysis, patients treated with omaveloxolone had lower mFARS scores after 3 years compared to a matched set of untreated patients from a natural history study. The Company noted that these exploratory analyses should be interpreted cautiously given the limitations of data.
The most common adverse reactions (incidence greater than or equal to 20% and greater than placebo) are elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.
The FDA previously granted Priority Review to omaveloxolone for this indication.
“Today’s approval of Skyclarys represents a significant milestone in our effort to advance research and achieve treatments for Friedreich’s ataxia,” said Jen Farmer, CEO at Friedreich’s Ataxia Research Alliance. “[…] Today, we celebrate the impact of an engaged patient community, and we are grateful to the FDA and Reata for working together on the approval of Skyclarys, the first therapy approved in the United States for adult and adolescent patients aged 16 years and older with Friedreich’s ataxia.”
Skyclarys will be supplied as 50mg capsules containing omaveloxolone in 90-count bottles.
- FDA approves first treatment for Friedreich’s ataxia. News release. Reata Pharmaceuticals. February 28, 2023. Accessed March 1, 2023. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-friedreichs-ataxia?utm_medium=email&utm_source=govdelivery.
- Reata Pharmaceuticals announces FDA approval of Skyclarys™ (Omavaloxolone), the first and only drug indicated for patients with Friedreich’s ataxia. News release. Reata Pharmaceuticals. February 28, 2023. Accessed March 1, 2023. https://www.reatapharma.com/investors/news/news-details/2023/Reata-Pharmaceuticals-Announces-FDA-Approval-of-SKYCLARYS-Omavaloxolone-the-First-and-Only-Drug-Indicated-for-Patients-with-Friedreichs-Ataxia/default.aspx.
- Skyclarys. Package insert. Reata Pharmaceuticals; 2023. Accessed March 1, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216718Orig1s000lbl.pdf.