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Quick highlights1,2

  • Treatment with SKYCLARYS resulted in lower modified Friedreich Ataxia Rating Scale (mFARS) scores, or less physical impairment, relative to placebo at week 48 in the pivotal MOXIe trial
  • Lower mFARS scores were observed in patients treated with SKYCLARYS after 3 years relative to a matched set of untreated patients from a natural history study*

These exploratory analyses should be interpreted cautiously given the limitations of data collected outside of a controlled study, which may be subject to confounding.

MOXIe trial

SKYCLARYS was studied in the MOXIe trial, the largest FA study of its kind1,2

Designed in consultation with clinical specialists and patient advocacy groups. The MOXIe trial was an international, double-blind, randomized, placebo-controlled, multicenter, registrational phase 2 trial. A total of 103 patients were randomized in a ratio of 1:1 to receive SKYCLARYS 150 mg once daily (n=51) or placebo (n=52).

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Reata's MOXIe trial results diagram
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The prespecified primary analysis

measured the change from baseline in the mFARS scores of patients after 48 weeks of treatment with SKYCLARYS vs placebo.†2

†In the full analysis population of patients without pes cavus (n=82).

SKYCLARYS slowed FA disease progression in the pivotal MOXIe trial1

Treatment with SKYCLARYS resulted in less physical impairment relative to placebo at week 48.
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IMPORTANT SAFETY INFORMATION

The most common adverse reactions (≥20% and greater than placebo) were elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.

Consistent results with SKYCLARYS1,2,12

Results from patient subgroups numerically favored SKYCLARYS over placebo:
  • Age (±18 years)
  • Sex
  • GAA repeat length (≥675)
  • Ambulatory status
  • Pes cavus
All 4 components of the mFARS assessment numerically favored SKYCLARYS over placebo.

Bulbar function

Lower limb coordination

Upper limb coordination

Upright stability

In adolescent patients aged 16 to 18 years treated with SKYCLARYS, a group difference of -4.21 points versus placebo was observed at week 48.‡
The MOXIe trial was not powered to detect a statistically significant difference among subgroups.
‡The MOXIe adolescent population, n=20; P=0.057.

3-Year Post Hoc Propensity-Matched Analysis: Lower mFARS scores were observed relative to a matched set of untreated patients from a natural history study1

These exploratory analyses should be interpreted cautiously given the limitations of data collected outside of a controlled study, which may be subject to confounding.
Diagram of Lower mFARS scores with SKYCLARYS (omaveloxolone) after 3 years
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Propensity matching is a method of comparing patients from a clinical trial with an external control by identifying comparable prognostic characteristics. It is informative in cases where a very long follow-up period is required to assess outcomes or when it is difficult to perform randomized controlled trials, such as in certain special patient populations.

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A post hoc propensity-matched analysis compared patients in the MOXIe open-label extension(OLE) with untreated patients who participated in a natural history study, the Friedreich Ataxia Clinical Outcome Measures Study (FA‑COMS).

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FA-COMS is a large, robust FA natural history study and has enrolled more than 1350 patients who have been followed for up to 15 years.

mFARS

What is mFARS?2,6

The mFARS is a clinically validated neurological assessment that provides a detailed evaluation of a patient’s status and is generally accepted as a clinical trial endpoint due to its correlation with disease progression. mFARS is not required to be used in the clinic in order to treat with SKYCLARYS.

mFARS range is 0-93 points

A higher score is associated with more severe disease.2,6

The mFARS is made up of 4 sections focused on functional abilities6:

Ability to complete many activities of daily living, such as getting dressed and eating

Predictor of time to loss of ambulation; the average score where loss of ambulation occurs is 65. A 2-point change in upright stability score may mean the difference between standing without support for 60 vs 30 seconds, or walking with mild vs severe impairment

Closely correlated with upright stability in predicting the likely rate of disease progression

Ability to speak clearly

While there is variability in progression, a patient’s mFARS score will worsen (increase) by about 2 points per year on average7

Patients with a younger age of onset may progress faster, worsening by an average of ~4 points per year.

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SKYCLARYS was not evaluated in patients younger than 16 years or older than 40 years of age.

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Review dosing and safety of SKYCLARYS
View dosing and safety

References:
1. Skyclarys. Prescribing Information. Reata Pharmaceuticals, Inc.; 2023. 2. Lynch DR, Chin MP, Delatycki MB, et al. Safety and efficacy of omaveloxolone in Friedreich ataxia (MOXIe study). Ann Neurol. 2021;89(2):212-225. 3. Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich’s ataxia: classical and atypical phenotypes. J Neurochem. 2013;126(suppl 1):103-117. 4. Schulz JB, Boesch S, Bürk K, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat Rev Neurol. 2009;5(4):222-234. 5. Rummey C, Farmer JM, Lynch DR. Predictors of loss of ambulation in Friedreich’s ataxia. EClinical Medicine. 2020;18:1-9. 6. Rummey C, Corben LA, Delatycki MB, et al. Psychometric properties of the Friedreich Ataxia Rating Scale. Neurol Genet. 2019;5(6):371. 7. Patel M, Isaacs CJ, Seyer L, et al. Progression of Friedreich ataxia: quantitative characterization over 5 years. Ann Clin Transl Neurol. 2016;3(9):684-694. 8. Lynch DR, Chin MP, Boesch S, et al. Efficacy of omaveloxolone in Friedreich’s ataxia: delayed-start analysis of the MOXIe extension. Mov Disord. Published online November 29, 2022. doi://10.1002/mds.29286 9. Galea CA, Huq A, Lockhart PJ, et al. Compound heterozygous FXN mutations and clinical outcome in Friedreich ataxia. Ann Neurol. 2016;79(3):485-495. 10. Fogel BL, Perlman S. Clinical features and molecular genetics of autosomal recessive cerebellar ataxias. Lancet Neurol. 2007;6(3):245-257. 11. Wallace SE, Bird TD. Molecular genetic testing for hereditary ataxia: what every neurologist should know. Neurol Clin Pract. 2018;8(1):27-32. 12. Lynch DR, Goldsberry A, Rummey C, et al. Direct utility of natural history data in analysis of clinical trials: propensity match-based analysis of omaveloxolone in Friedreich ataxia using the FA-COMS dataset. Preprint. Posted online August 16, 2022. medRxiv 2022.08.12.22278684. doi: https://doi.org/10.1101/2022.08.12.22278684 13. Beaulieu-Jones BK, Finlayson SG, Yuan W, et al. Examining the use of real-world evidence in the regulatory process. Clin Pharmacol Ther. 2020;107(4):843-852.

Important Safety Information

WARNINGS AND PRECAUTIONS

Elevation of Aminotransferases: Treatment with SKYCLARYS can cause an elevation in hepatic transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). The incidence of elevations of ALT or AST above 5 times and 3 times the upper limit of normal (ULN) was 16% and 31%, respectively, in patients treated with SKYCLARYS. There were no cases of concomitant elevation of transaminases and total bilirubin observed. Maximum increases in ALT and AST occurred within 12 weeks after starting SKYCLARYS. Increases in serum aminotransferases were generally asymptomatic and reversible following discontinuation of SKYCLARYS. Patients with clinically significant liver disease were excluded from the pivotal study.

Monitor ALT, AST, and total bilirubin prior to initiation of SKYCLARYS, every month for the first 3 months of treatment, and periodically thereafter. If transaminases increase to levels greater than 5 times the ULN, or greater than 3 times the ULN with evidence of liver dysfunction (e.g., elevated bilirubin), immediately discontinue SKYCLARYS and repeat liver function tests as soon as possible. If transaminase levels stabilize or resolve, SKYCLARYS may be reinitiated with an appropriate increased frequency of monitoring of liver function.

Elevation of B-Type Natriuretic Peptide: Treatment with SKYCLARYS can cause an increase in B-type natriuretic peptide (BNP), a marker of cardiac function. A total of 14% of patients treated with SKYCLARYS had an increase from baseline in BNP value above the ULN (100 pg/mL), compared to 4% of patients who received placebo. The incidence of elevation of BNP above 200 pg/mL was 4% in patients treated with SKYCLARYS. Cardiomyopathy and cardiac failure are common in patients with Friedreich ataxia. Patients were excluded from the pivotal study if they had BNP levels > 200 pg/mL prior to study entry, or a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease, with the exception of mild to moderate cardiomyopathy associated with Friedreich ataxia. Whether the elevations in BNP are related to SKYCLARYS or cardiac disease associated with Friedreich ataxia is unclear.

Elevations in BNP may indicate cardiac failure and should prompt an evaluation of cardiac function. Check BNP prior to initiation of SKYCLARYS. Monitor patients for the signs and symptoms of fluid overload, such as sudden weight gain (3 pounds or more of weight gain in one day, or 5 pounds or more of weight gain in a week), peripheral edema, palpitations, and shortness of breath. If signs and symptoms of fluid overload develop, worsen, or require hospitalization, evaluate BNP and cardiac function, and manage appropriately. Management of fluid overload and heart failure may require discontinuation of SKYCLARYS.

Lipid Abnormalities: Treatment with SKYCLARYS can cause changes in cholesterol. In the pivotal study, 29% of patients treated with SKYCLARYS reported elevated cholesterol above ULN at one or more time points. Mean increases were observed within 2 weeks of initiation of SKYCLARYS and returned to baseline within 4 weeks of discontinuing treatment. A total of 16% of patients treated with SKYCLARYS had an increase in low-density lipoprotein cholesterol (LDL-C) from baseline, compared to 8% of patients who received placebo. The mean increase in LDL-C for all SKYCLARYS-treated patients was 23.5 mg/dL at 48 weeks. A total of 6% of patients treated with SKYCLARYS had decreases in high-density lipoprotein cholesterol (HDL-C) from baseline compared to 4% of patients who received placebo. The mean decrease in HDL-C for all SKYCLARYS-treated patients was 5.3 mg/dL at 48 weeks.

Assess lipid parameters prior to initiation of SKYCLARYS and monitor periodically during treatment. Manage lipid abnormalities according to clinical guidelines.

CONTRAINDICATIONS

None.

ADVERSE REACTIONS

Adverse reactions reported in 10% or more of patients and greater than placebo were elevated liver enzymes (AST/ALT) (37%), headache (37%), nausea (33%), abdominal pain (29%), fatigue (24%), diarrhea (20%), musculoskeletal pain (20%), oropharyngeal pain (18%), influenza (16%), vomiting (16%), muscle spasms (14%), back pain (13%), decreased appetite (12%), rash (10%).

DRUG INTERACTIONS

  • Moderate or Strong CYP3A4 Inhibitors: Avoid concomitant use. Consider SKYCLARYS dosage reduction with monitoring if use is unavoidable.
  • Moderate or Strong CYP3A4 Inducers: Avoid concomitant use.
  • Hormonal Contraceptives: Counsel females to use an alternative contraceptive method (e.g., non-hormonal intrauterine system) or additional non-hormonal contraceptive (e.g., condoms) during concomitant use and for 28 days after discontinuation of SKYCLARYS.

This is not a complete list of potential drug interactions.

Specific Population: The effects on milk production and the breastfed infant are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SKYCLARYS and any potential adverse effects on the breastfed infant from SKYCLARYS or from the underlying maternal condition.

To report SUSPECTED ADVERSE REACTIONS, contact Reata Pharmaceuticals, Inc. at 1-800-314-3934 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

INDICATION

SKYCLARYS is indicated for the treatment of Friedreich ataxia in adults and adolescents aged 16 years and older.

For more information about SKYCLARYS, please see the full Prescribing Information.

US-SKY-2300055 v4.0

Skyclarys (omaveloxolone) 50mg capsules