Omaveloxolone: The First Approved Drug for Friedreich Ataxia

Table of Contents

1. Omaveloxolone at a Glance
2. Frataxin Loss and a Weakened Antioxidant Defence
3. How Omaveloxolone Switches On Nrf2
4. MOXIe Part 1: Finding the Dose
5. MOXIe Part 2: The 48-Week Placebo-Controlled Trial
6. The High-Arched-Foot (Pes Cavus) Subgroup
7. The Open-Label Extension and the 3-Year Matched Comparison
8. Results Since Approval
9. The Approvals, the Label and the Dose
10. Liver Enzymes, a Heart-Strain Marker and Cholesterol
11. Side Effects and How Often They Occurred
12. Drug Interactions, Food and Hormonal Contraception
13. Pregnancy, Breastfeeding and Animal Findings
14. Other Diseases Where It Was Tested
15. What Is Not Known
16. Regulatory Documents
17. Key Research Papers
18. Connections
19. Featured Videos

Omaveloxolone at a Glance

• What it is: an orally active, small-molecule, semi-synthetic triterpenoid, as a 2023 drug profile describes it: a laboratory-modified member of a chemical family found in plants. It comes as 50 mg capsules.
• What it is approved for: Friedreich ataxia in adults and adolescents aged 16 years and older, in the United States and in the European Union.
• U.S. approval: February 28, 2023, as a new molecular entity under priority review (New Drug Application 216718). The FDA notice lists orphan drug, fast track, priority review and rare pediatric disease designations.
• European approval: the European Medicines Agency's committee gave a positive opinion on December 14, 2023, and the marketing authorisation was issued on February 9, 2024. The medicine had been designated an orphan medicine on June 27, 2018.
• Dose on the U.S. label: 150 mg, which is three capsules, once a day on an empty stomach.
• Label warnings: rises in liver enzymes, rises in a blood marker of heart strain, and cholesterol changes. The label lists no contraindications.
• Main evidence: the MOXIe trial, run in two parts, plus its open-label extension.

Frataxin Loss and a Weakened Antioxidant Defence

In Friedreich ataxia a repeat expansion in the FXN gene lowers the amount of frataxin, a protein inside mitochondria, the energy-producing parts of the cell. The disease page explains how that leads to iron building up in mitochondria and to damage from reactive oxygen. Large sensory nerve cells, the spinal cord and the heart muscle are hit hardest.

Cells normally answer oxidative stress by switching on a set of protective genes. The master switch for that answer is a protein called nuclear factor erythroid 2-related factor 2 (Nrf2). When a cell is under oxidative strain, Nrf2 moves into the cell nucleus and turns on genes for antioxidant enzymes.

Several laboratory studies found that this switch is itself weakened in Friedreich ataxia:

• In 2009, Paupe and colleagues found that skin cells (fibroblasts) grown from patients were unusually sensitive to oxidative damage because Nrf2 signalling was impaired, so the antioxidant enzymes were not properly switched on.
• In 2013, D'Oria and colleagues silenced the frataxin gene in cultured motor nerve cells and found lower Nrf2 messenger RNA and a faulty Nrf2 response to oxidising chemicals.
• The 2019 report of MOXIe part 1 summed up earlier work this way: suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction and reduced energy (ATP) production.

The European Medicines Agency's public summary puts it plainly: Nrf2 levels and activity appear to be reduced in patients with Friedreich's ataxia. That is the reasoning behind the drug. If the cell's own antioxidant switch is stuck, a drug that pushes it back on might slow the damage, even though the missing frataxin is still missing.

How Omaveloxolone Switches On Nrf2

Inside a resting cell, Nrf2 is constantly tagged for destruction and broken down. A 2023 drug profile in the journal Drugs states that omaveloxolone may activate the Nrf2 pathway by blocking that tagging (ubiquitination) and breakdown, so more Nrf2 survives to reach the nucleus.

The U.S. label is careful on this point. It states that the precise mechanism by which omaveloxolone works in Friedreich ataxia is unknown, and that the drug has been shown to activate the Nrf2 pathway in laboratory tests and in animals and humans. The MOXIe part 1 report also describes it as a suppressor of NF-kB, a switch for inflammation.

Laboratory findings that support the idea:

• In a 2018 study of nerve cells taken from two Friedreich ataxia mouse models, and of skin cells from patients, omaveloxolone restored the activity of complex I, the first step of the mitochondrial energy chain. In the patient cells it also lowered lipid damage and mitochondrial reactive oxygen and raised glutathione, the cell's main antioxidant, and it protected the cells from death after a hydrogen peroxide challenge. These were cell results.
• In MOXIe part 1, blood markers that respond to Nrf2 activity, ferritin and gamma-glutamyl transferase, changed most at doses of 80 and 160 mg a day in people with the disease.

Not every animal result has been positive. A 2025 study of an inducible Friedreich ataxia mouse found no benefit from omaveloxolone or from another Nrf2-inducing drug, dimethyl fumarate, on any of several movement, gait and sensation tests, although male mice showed more decline and somewhat better response. A second 2025 study in mice with severe frataxin-deficient heart disease is described under Other Diseases Where It Was Tested.

MOXIe Part 1: Finding the Dose

MOXIe began as a dose-finding study. Sixty-nine people with Friedreich ataxia were randomized 3 to 1 to omaveloxolone or placebo, in groups of eight, at doses from 2.5 to 300 mg a day, for 12 weeks. The results were published in 2019.

• The drug was well tolerated, and side effects were generally mild.
• The main outcome, the peak workload people could reach in a maximal exercise test, did not change significantly: 0.9 watts after correcting for placebo.
• The modified Friedreich's Ataxia Rating Scale (mFARS) was a secondary outcome. At 160 mg a day the ataxia score improved by 3.8 points from the starting value (P = 0.0001) and by 2.3 points compared with placebo (P = 0.06, just short of the usual threshold).
• The improvement was larger in people who did not have a high-arched foot deformity (pes cavus). In them, 160 mg a day improved the ataxia score by 6.0 points from the starting value (P < 0.0001) and by 4.4 points compared with placebo (P = 0.01).

The authors chose 150 mg a day for the next stage. The pes cavus finding shaped how part 2 was designed and analysed.

MOXIe Part 2: The 48-Week Placebo-Controlled Trial

Part 2 was an international, double-blind, randomized, placebo-controlled trial at 11 institutions in the United States, Europe and Australia (registered as NCT02255435). The authors call it a registrational phase 2 trial, meaning it was designed to support approval. It was published in 2021 in the Annals of Neurology.

Who took part

People aged 16 to 40 with genetically confirmed Friedreich ataxia and an ataxia score between 20 and 80 could join. Of 155 people screened, 103 were randomized: 51 to omaveloxolone 150 mg a day and 52 to placebo. According to the label, they also had to be able to complete an exercise test and have a heart pumping fraction (left ventricular ejection fraction) of at least 40%. The mean age was 24, 53% were male and 97% were White. The full paper reports that 92% could still walk.

The rating scale

The ataxia scale scores four areas: speech and swallowing, arm and hand coordination, leg coordination, and upright stability. The maximum score is 99, and a lower score means less impairment. In untreated people the score rises over time as the disease progresses.

The main result

The pre-planned main analysis covered the 82 people without pes cavus who had at least one follow-up visit: 40 on the drug and 42 on placebo. After 48 weeks:

• The ataxia score fell by 1.55 points on omaveloxolone, an improvement.
• It rose by 0.85 points on placebo, a worsening.
• The difference was 2.40 points in favour of the drug (p = 0.014).

The label gives the same analysis as minus 1.56 and minus 2.41 points (p = 0.0138), a rounding difference. The full paper reports that the drug improved all four parts of the scale, with the largest effect on upright stability, and that the placebo group's upright stability worsened steadily.

Other measures

The secondary outcomes were tested in a fixed order, and the first one in line, the patient's own impression of change, did not differ significantly between the groups. Under the trial's statistical rules, that meant none of the secondary measures counted as significant, including the clinician's impression of change, a peg-board hand test, a timed 25-foot walk, falls, exercise capacity and an activities-of-daily-living score. The authors note that the trial was not powered for these. In a later count of individual responders, more people on the drug improved, and fewer worsened, on the ataxia score, the daily-living score and the patient impression.

Things that complicate the picture

• The drug group started out somewhat sicker: 48% had a history of heart muscle disease against 29% on placebo, and they had longer gene repeats on average. In analyses done afterwards that adjusted for these, the difference between groups grew, to 2.65 points when heart disease history was included.
• In the 20 people under 18, placebo worsened by 2.52 points and the drug improved by 1.63 points, a difference of 4.16 points that did not reach significance (p = 0.057).
• The authors list the small size, the modest length and limits on how far the results apply to other groups as limitations. Most participants were in the middle stages of the disease.
• The trial was paid for by the drug's developer, and several authors were its employees, as the paper's conflict-of-interest statement records.

The High-Arched-Foot (Pes Cavus) Subgroup

Pes cavus is a high-arched foot that cannot flatten, common in Friedreich ataxia. Because part 1 had shown a weaker response in people with it, part 2 handled them separately:

• How it was defined: a flashlight shone from the side could be seen under the arch while the person stood barefoot. A positive test on one foot counted.
• How many: enrolment of people with pes cavus was capped at 20%, and randomization was balanced for it. Twenty people had it, 10 in each group. People with particularly severe foot deformity were excluded.
• The main analysis left them out, as planned before the trial.
• The analysis of all 103 randomized people, pes cavus included, showed a smaller difference of 1.93 points in favour of the drug (p = 0.034) in the paper. The label reports it as 1.94 points (p = 0.0331) and calls it nominally significant.

The authors wrote that, as in part 1, the drug improved the ataxia score less in people with pes cavus, and that the repeat of the finding suggests it is real, although the reason is not obvious. They raised several possibilities: fixed foot deformity that does not easily reverse, a subgroup affected in other ways, or simply that people with pes cavus, as defined in the trial, were a more severely affected group.

The European Medicines Agency's summary explains the exclusion from the main analysis by the lack of a standard way to grade pes cavus severity and its possible effect on the score. The agency nevertheless considered that the benefits also applied to these patients and to those with more severe disease who had been excluded from the trial.

The Open-Label Extension and the 3-Year Matched Comparison

After part 1 or part 2, participants could take omaveloxolone in an open-label extension, where everyone knew they were on the drug.

The delayed-start analysis (2023)

This compared people who had been on the drug from the start of part 2 with people who switched from placebo to the drug in the extension. The question was whether the late starters would catch up. Among those in the extension, the gap between groups at the end of part 2 was 2.17 points. After 72 weeks in the extension it was 2.91 points, so the late starters did not close the gap. People who had been on the drug since part 2 showed no worsening of their ataxia score, measured from their extension starting point, through 144 weeks. The authors read this as a lasting effect on the course of the disease.

The 3-year propensity-matched comparison (2024): not randomized

Here people in the extension were compared with untreated people from the Friedreich ataxia Clinical Outcome Measures Study, a long-running natural-history study. Each treated person was paired with an untreated person who was similar in sex, age, age at onset, starting ataxia score and walking score.

• In the main pooled group of 136 people on each side, by year 3 the ataxia score worsened by 6.6 points in the untreated group and by 3 points in the treated group.
• The difference was 3.6 points, with a nominal p value of 0.0001.
• The treated group had a smaller change in every year and every analysis group.

This was not a randomized comparison. The FDA label describes it as a post hoc, exploratory analysis to be interpreted cautiously, because data collected outside a controlled study may be affected by confounding, meaning hidden differences between the groups. Two of its authors were employees of the developer, as its conflict-of-interest statement records.

Results Since Approval

The drug became available in the United States in July 2023, according to a clinic in Philadelphia that reported its first year. Smaller clinic reports and reviews have followed.

• Philadelphia, first year (2025): 236 people obtained the drug. Side effects were noted in 23.8%, most often stomach upset, headache and fatigue. Twenty-one people (8.9%) stopped the drug for good during the first year. Some liver enzyme value was above the normal limit at least once in 56.6%, mostly in the first 3 months; after 6 months only 8.6% had raised values. Rises were generally under 3 times the normal limit and fell with a pause or a lower dose. The heart-strain marker was generally unchanged, and cholesterol rises were mild.
• Palermo, Italy (2025 and 2026): 20 adults with a mean age of about 41 and about 25 years of disease. At 24 weeks there were no significant side effects or stoppages, but 50% had a temporary liver enzyme rise; heart function, the heart-strain marker and lipids were stable; the rating scales did not change significantly. At 48 weeks the same group showed a falling level of interleukin-6, an inflammation messenger, with one stoppage.
• Turin, Italy, advanced disease (2026): 27 people with advanced disease, including people who could no longer walk; the 26 analysed had a median age of 42.5 and a median disease length of 24.5 years. Among the 26 who stayed on the drug for at least 3 months, the ataxia score improved by 1.5 points (P = 0.007), and 42.3% felt they had improved. No serious side effects occurred. The follow-up was 3 to 6 months.
• Pooled analysis (2026): a single-arm meta-analysis of four studies with 248 people found improvement in the controlled trials (2.19 points) and slow worsening in the real-world studies (2.85 points), which the authors judged slower than natural history. There was no untreated comparison group in the real-world studies.
• Cochrane review (2026): this review pooled randomized trials of several drugs for Friedreich ataxia, omaveloxolone among them, lasting at least 12 months. Across seven trials and 513 people, the drugs as a group probably made little or no difference to ataxia scale scores compared with placebo (moderate-certainty evidence). The pooled figure covers all the drugs together, not omaveloxolone alone.

The Approvals, the Label and the Dose

The FDA approval notice of February 28, 2023 describes the drug as the first treatment for Friedreich ataxia, based on the 48-week trial and the open-label extension. It notes that 9 of the participants (18%) were younger than 18. This page reads the label version effective April 6, 2026, through openFDA.

The dose as the label gives it

• 150 mg (three 50 mg capsules) once a day, on an empty stomach: at least 1 hour before or 2 hours after eating.
• The capsules are swallowed whole, not crushed or chewed. For people who cannot swallow them, the capsules may be opened and the entire contents sprinkled onto 2 tablespoons (30 mL) of applesauce and swallowed right away. The label states that the contents are not to be mixed with milk or orange juice, and that the drug is not for feeding tubes.
• A missed dose is skipped; the next dose is taken at the usual time the next day, and the label states that a double dose is not to be taken.
• Moderate liver impairment (Child-Pugh class B): 100 mg once a day, lowered to 50 mg if side effects appear. Severe liver impairment (class C): the label advises against use. Mild impairment: no change.

Why food and applesauce matter

• A high-fat meal raised the drug's peak blood level by about 350% but its total exposure by only about 15%, according to the label. A 2024 modelling study explained this by faster dissolution with bile salts and more breakdown in the gut wall when the drug is taken with fat.
• In a 2024 study of 32 healthy volunteers, sprinkling the capsule contents on applesauce gave the same peak and total exposure as intact capsules; the drug was absorbed somewhat faster (median peak at 6 hours instead of 10). The authors note this option was added because some people with the disease have swallowing difficulty.
• The drug stays in the body a long time: the label gives a mean half-life of 57 hours (range 32 to 90). About 92% of a dose leaves in the stool.

Heart rhythm

A 2025 study in 30 healthy adults gave a single 450 mg dose, three times the approved dose, with a high-fat meal. It found no clinically significant lengthening of the QT interval, the part of the heart tracing that some drugs prolong. The label reports the same result.

Monitoring the label sets out

The label states that liver enzymes, bilirubin, the heart-strain marker and blood lipids are measured before the drug is started and during treatment. Details follow in the next section.

Liver Enzymes, a Heart-Strain Marker and Cholesterol

Liver enzymes

The most frequent laboratory change is a rise in two liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). According to the label, in the main trial:

• 31% of people on the drug had a rise above 3 times the upper limit of normal, and 16% above 5 times.
• No one had a liver enzyme rise together with a bilirubin rise, the combination that signals serious liver injury.
• The highest values came within 12 weeks of starting. The rises were generally without symptoms and went away after the drug was stopped.
• People with significant liver disease were not in the trial.

The trial paper adds that 15 people on the drug (29%) and none on placebo reached 3 times the normal limit for ALT, and that 12 of those 15 were back to normal within 4 weeks of stopping. The authors suggested that the rises may reflect Nrf2 switching on the genes for these enzymes rather than liver damage, since the drug and a related compound raised the enzymes' gene activity in cells.

The label sets out testing of ALT, AST and total bilirubin before starting, every month for the first 3 months and from time to time after that. It instructs stopping the drug at once if the enzymes rise above 5 times normal, or above 3 times normal with signs of liver dysfunction such as raised bilirubin, and allows a restart with closer testing once the values settle. A 2025 review based on the views of four Friedreich ataxia specialists and a liver specialist proposed, for routine clinic follow-up, pausing treatment at 3 times normal even without other signs, then restarting with step-by-step dose increases and testing every 2 weeks for about 3 months.

B-type natriuretic peptide (BNP)

B-type natriuretic peptide is released by a strained heart. According to the label, 14% of people on the drug had a rise from their starting value to above 100 pg/mL, against 4% on placebo, and 4% on the drug had a level above 200 pg/mL. People with values above 200 pg/mL, or with significant heart disease other than mild to moderate Friedreich-related heart muscle disease, were kept out of the trial. The label states that it is unclear whether the rises came from the drug or from the heart disease that is part of Friedreich ataxia, and that raised values may indicate heart failure.

The label lists signs of fluid overload that it says call for a check of this marker and of heart function: sudden weight gain of 3 pounds or more in a day or 5 pounds or more in a week, swelling of the legs or feet, palpitations, and shortness of breath. It states that managing fluid overload and heart failure may require stopping the drug. In the Philadelphia first-year series the marker was generally unchanged.

Cholesterol

According to the label, in the main trial:

• 29% of people on the drug had total cholesterol above the normal limit at least once.
• 16% had a rise in low-density lipoprotein (LDL) cholesterol, against 8% on placebo. The mean rise in low-density lipoprotein cholesterol was 23.5 mg/dL at 48 weeks.
• 6% had a fall in high-density lipoprotein (HDL) cholesterol, against 4% on placebo, with a mean fall of 5.3 mg/dL.
• The changes began within 2 weeks and returned to baseline within 4 weeks of stopping.

A 2026 study from Vienna followed 17 adults for a year after starting the drug. Low-density lipoprotein cholesterol rose by 35 to 50 mg/dL and apolipoprotein B by 20 to 25 mg/dL, and stayed up, while high-density lipoprotein cholesterol and triglycerides stayed stable. The authors described a lasting shift toward a more artery-clogging lipid profile and called for further study of long-term heart and blood-vessel risk. Cholesterol rises were also among the reports in the FDA's adverse event database.

Side Effects and How Often They Occurred

The label lists the side effects that occurred in at least 10% of people on omaveloxolone in the main trial, and more often than on placebo:

• Raised liver enzymes: 37% on the drug, 2% on placebo
• Headache: 37% and 25%
• Nausea: 33% and 13%
• Abdominal pain: 29% and 6%
• Fatigue: 24% and 14%
• Diarrhea: 20% and 10%
• Muscle and bone pain: 20% and 15%
• Sore mouth and throat: 18% and 6%
• Influenza: 16% and 6%
• Vomiting: 16% and 12%
• Muscle spasms: 14% and 6%
• Back pain: 13% and 8%
• Decreased appetite: 12% and 4%
• Rash: 10% and 4%

Other findings:

• The trial paper reports serious adverse events in 10% on the drug and 6% on placebo, and stopping because of a side effect in 8% and 4%.
• Adults on the drug lost some weight on average, more so if they were overweight at the start, according to the paper. The European summary lists decreased weight among the most common side effects.
• The label adds allergic reactions (hives, rash) reported after approval.
• A 2025 analysis of 820 reports in the FDA Adverse Event Reporting System found raised liver enzymes the strongest signal, followed by fatigue, nausea, headache and raised cholesterol. It also flagged possible new signals, including urinary tract infection, diabetes, abnormal urine smell, atrial flutter and urosepsis. Reports of this kind show which problems people reported, not that the drug caused them.

Drug Interactions, Food and Hormonal Contraception

The liver enzyme cytochrome P450 3A4 (CYP3A4) breaks down most of the drug. That makes it sensitive to other medicines that block or speed up this enzyme. A 2025 report described two interaction studies in healthy volunteers.

Medicines that raise or lower omaveloxolone

• Strong blockers of the enzyme: itraconazole, an antifungal, raised the drug's peak level about 3-fold and total exposure about 4-fold. The label advises against the combination; if it cannot be avoided, it gives a dose of 50 mg once a day with close watching for side effects.
• Moderate blockers: verapamil raised exposure about 1.25-fold. The label advises against the combination; if it cannot be avoided, it gives 100 mg once a day, lowered to 50 mg if side effects appear.
• Moderate or strong speeders-up (inducers): efavirenz lowered the peak by 38% and total exposure by 48%. The label advises against combining omaveloxolone with moderate or strong inducers, since lower levels may make it less effective.
• The label's patient information tells patients to stay away from grapefruit and grapefruit juice, and names St. John's wort as an example of an herbal product to mention to the prescriber.

Medicines that omaveloxolone lowers

Omaveloxolone itself mildly speeds up two drug-processing enzymes. It lowered exposure to midazolam by about 45%, repaglinide by about 35% and rosuvastatin by about 30%, according to the label. It made no important difference to digoxin or metformin.

Hormonal contraception

Because it speeds up the breakdown of other medicines, omaveloxolone may make hormonal contraceptives less effective. The label advises against using it together with combined hormonal contraceptives (pill, patch or ring), implants and progestin-only pills. It describes switching to, or adding, a non-hormonal method, such as a non-hormonal intrauterine device or condoms, during treatment and for 28 days after stopping.

Pregnancy, Breastfeeding and Animal Findings

• Pregnancy: the label states that there are no adequate data in pregnant women and that, based on animal data, the drug may cause harm to the unborn baby. In rats and rabbits, the drug given in pregnancy caused loss of embryos, poor growth, and in rat offspring deaths, poor growth, and learning, memory and activity problems, at blood levels similar to or below those in people. In the rat study through pregnancy and nursing, no dose was free of effects on the offspring. A pregnancy exposure registry follows outcomes in women who take the drug while pregnant.
• Breastfeeding: there are no data on the drug in human milk. It passed into the milk of nursing rats. A study of how the drug moves into breast milk in healthy women is listed as completed on ClinicalTrials.gov (NCT06612879).
• Fertility: in rats given the drug before and during mating, the highest dose caused embryo loss.
• Cancer studies: in a 2-year study in rats, female rats at the highest dose (1.9 times the human exposure) had more bile-duct tumours of the liver (cholangioma and cholangiocarcinoma). A 26-week study in a special strain of mice found no increase in tumours.
• Gene damage tests: negative in a bacterial test, positive in a test on human blood cells in the laboratory, and negative in two further tests, one in rats.

Other Diseases Where It Was Tested

• Advanced cancer (first human trial, 2017): the drug, then called RTA 408, was first given by mouth to people with advanced melanoma or lung cancer, at up to 15 mg a day. No dose-limiting side effects were found, and there were no confirmed tumour responses.
• Mitochondrial myopathy (MOTOR trial, 2020): 53 people with mitochondrial myopathy, a muscle disease caused by faulty mitochondria, took doses from 5 to 160 mg or placebo for 12 weeks. Peak exercise workload and 6-minute walking distance did not change. At 160 mg, heart rate during moderate exercise was 12 beats per minute lower than on placebo, and blood lactate was lower, which were exploratory measures.
• Frataxin-deficient heart disease, in mice (2025): in mice whose heart muscle lacked frataxin, omaveloxolone improved the heart's pumping and markers of heart failure, but it did not reduce thickening or scarring of the heart, did not prevent early death, and was linked to earlier death in female mice. The authors called for more study of the deaths in the female mice.

Laboratory and animal studies have also tested the drug in many other conditions. Those results come from cells and animals, and the drug is approved only for Friedreich ataxia.

What Is Not Known

• Long-term outcomes: the only placebo-controlled evidence lasts 48 weeks. Whether the drug changes the things that matter most over decades, such as keeping the ability to walk, heart failure, and length of life, has not been tested in a randomized trial. The 3-year comparison with natural-history data is not randomized. A long-term safety study in people aged 16 and older is recruiting (NCT06623890).
• Children under 16: the label states that safety and effectiveness have not been established below age 16. The FDA approval notice states that the disease tends to develop in children and teenagers. ClinicalTrials.gov lists a phase 3 study in children and teens aged 2 to 15 (NCT06953583) and a phase 1 study of how the drug is handled in the same age range (NCT06054893); no results were posted when this page was written.
• Effects on the heart: heart disease is the leading cause of death in Friedreich ataxia. MOXIe found no changes on heart ultrasound over 48 weeks, but people with significant heart disease were excluded. The label states that it is unclear whether the rises in the heart-strain marker come from the drug or from the disease. In mice the drug improved heart pumping but not survival. The lasting rise in low-density lipoprotein cholesterol adds a further unknown for long-term blood-vessel health.
• Advanced disease: the trial took people aged 16 to 40 who could complete an exercise test. The European Medicines Agency named the exclusion of people with severe forms of the disease as an uncertainty. Reports in older people with advanced disease are small and short.
• Older adults and kidney disease: the label notes that the trials included no one aged 65 or over, and that the effect of moderate or severe kidney impairment on blood levels is unknown.
• How it works in this disease: the label states that the precise mechanism is unknown.

Regulatory Documents

1. U.S. National Library of Medicine, DailyMed. Omaveloxolone capsules: prescribing information (read through the openFDA label record effective April 6, 2026, November 2026). DailyMed label
2. U.S. Food and Drug Administration, Drugs@FDA. New Drug Application 216718: original approval February 28, 2023, priority review, new molecular entity. Drugs@FDA record
3. U.S. Food and Drug Administration. FDA approves first treatment for Friedreich's ataxia. February 28, 2023. FDA approval notice
4. European Medicines Agency. Omaveloxolone: European public assessment report, medicine overview and product information. Marketing authorisation issued February 9, 2024. EMA assessment report page
5. ClinicalTrials.gov. MOXIe, NCT02255435. NCT02255435
6. ClinicalTrials.gov. Phase 3 study in children and teens aged 2 to 15, NCT06953583. NCT06953583
7. ClinicalTrials.gov. Long-term safety study, NCT06623890. NCT06623890

Key Research Papers

1. Lynch DR, Chin MP, Delatycki MB, Subramony SH, Corti M, Hoyle JC, Boesch S, Nachbauer W, Mariotti C, Mathews KD, Giunti P, Wilmot G, Zesiewicz T, Perlman S, Goldsberry A, O'Grady M, Meyer CJ. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021;89(2):212-225. PubMed PMID: 33068037
2. Lynch DR, Farmer J, Hauser L, Blair IA, Wang QQ, Mesaros C, Snyder N, Boesch S, Chin M, Delatycki MB, Giunti P, Goldsberry A, Hoyle C, McBride MG, Nachbauer W, O'Grady M, Perlman S, Subramony SH, Wilmot GR, Zesiewicz T, Meyer C. Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Ann Clin Transl Neurol. 2019;6(1):15-26. PubMed PMID: 30656180
3. Lynch DR, Chin MP, Boesch S, Delatycki MB, Giunti P, Goldsberry A, Hoyle JC, Mariotti C, Mathews KD, Nachbauer W, O'Grady M, Perlman S, Subramony SH, Wilmot G, Zesiewicz T, Meyer CJ. Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed-Start Analysis of the MOXIe Extension. Mov Disord. 2023;38(2):313-320. PubMed PMID: 36444905
4. Lynch DR, Goldsberry A, Rummey C, Farmer J, Boesch S, Delatycki MB, Giunti P, Hoyle JC, Mariotti C, Mathews KD, Nachbauer W, Perlman S, Subramony SH, Wilmot G, Zesiewicz T, Weissfeld L, Meyer C. Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data. Ann Clin Transl Neurol. 2024;11(1):4-16. PubMed PMID: 37691319
5. Zahir H, Murai M, Wu L, Valentine M, Hynes SM. Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study. Clin Transl Sci. 2025;18(2):e70139. PubMed PMID: 39976332
6. Zahir H, Murai M, Wu L, Valentine M, Hynes S. Clinical Assessment of the Drug-Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants. J Clin Pharmacol. 2025;65(6):715-730. PubMed PMID: 39920097
7. Hynes SM, Goldsberry A, Henneghan PD, Murai M, Shinde A, Wells JA, Wu L, Wu T, Zahir H, Khan S. Relative Bioavailability of Omaveloxolone When Capsules Are Sprinkled Over and Mixed in Applesauce Compared With Administration as Intact Omaveloxolone Capsules: A Phase 1, Randomized, Open-Label, Single-Dose, Crossover Study in Healthy Adults. J Clin Pharmacol. 2024;64(10):1304-1311. PubMed PMID: 38837775
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1. PubMed: omaveloxolone Friedreich ataxia
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Connections

• Drugs — every drug page on the site
• Friedreich's Ataxia — the disease this drug treats
• Cerebellar Ataxia — the wider family of ataxias and their treatments
• Hypertrophic Cardiomyopathy — the heart muscle thickening common in Friedreich ataxia
• Oxidative Stress — free radicals and the body's antioxidant defences
• Sulforaphane and Nrf2 — a food compound that acts on the same switch
• Vitamin E Deficiency: Nerve Damage and Ataxia — a treatable ataxia that can resemble Friedreich ataxia
• Neurology — all nervous system conditions

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