SKYCLARYS dosing and safety

Understand dosing and safety behind this once-daily treatment1

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Quick highlights1

  • SKYCLARYS is a once-daily oral prescription medicine
  • Some inhibitors and even foods like grapefruit can interfere with treatment. See more details below
  • Increases in ALT/AST were generally asymptomatic and reversible. Maximum increases in ALT and AST occurred within 12 weeks of starting SKYCLARYS

SKYCLARYS is a once-daily oral prescription medicine1

The recommended dose is 150 mg taken as 3 capsules (50 mg each) once daily.1

For patients taking SKYCLARYS1:

  • Take on an empty stomach 1 hour before eating
  • Swallow SKYCLARYS capsules whole. Do not crush or chew
  • Avoid grapefruit and grapefruit juice
  • If a dose of SKYCLARYS is missed, take the next dose at its scheduled time the following day. A double dose should not be taken to make up for a missed dose
  • Discuss all medications they are taking, including other prescription medications, non-prescription medications, or herbal products (eg, St. John’s wort)

For patients who are unable to swallow whole capsules1:

  • SKYCLARYS capsules may be opened and the entire contents of both halves of the capsule sprinkled onto 2 tablespoons (30 mL) of applesauce
  • Stir the mixture until homogenous
  • Swallow all the drug/applesauce mixture immediately
  • Do not store the mixture for future use
  • Contents of the SKYCLARYS capsules should not be mixed with milk or orange juice
  • Not for enteral feeding tube administration

Additional dosing and administration considerations for patients taking SKYCLARYS1:

For additional information about SKYCLARYS dosing as it relates to concomitant use with strong or moderate CYP3A4 inhibitors/inducers, patients with hepatic impairment, and the use of hormonal contraceptives, please see the full Prescribing Information.

Consult the full Prescribing Information for specific dosing considerations for these patients.

Warnings and precautions1

Elevation of aminotransferases

Treatment with SKYCLARYS can cause an elevation in hepatic transaminases (ALT and AST).

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 (eg, 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.

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.

Elevation of B-type natriuretic peptide (BNP)

Treatment with SKYCLARYS can cause an increase in BNP, a marker of cardiac function. 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. Management of fluid overload and heart failure may require discontinuation of SKYCLARYS.

Lipid abnormalities

Treatment with SKYCLARYS can cause changes in cholesterol.

Mean increases were observed within 2 weeks of initiation of SKYCLARYS and returned to baseline within 4 weeks of discontinuing treatment. Assess lipid parameters prior to initiation of SKYCLARYS and monitor periodically during treatment.

ALT=alanine aminotransferase,

AST=aspartate aminotransferase,

ULN=upper limit of normal.

Safety data from the MOXIe trial1,2

Adverse events were generally considered mild to moderate.

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.1

Adverse reactions reported in ≥10% of patients and greater than placebo.

  • 3 patients reported serious adverse events (SAEs) while taking SKYCLARYS2
  • 2 patients reported SAEs ~2 weeks after discontinuation2
  • 4 patients in the SKYCLARYS group and 2 patients in the placebo group discontinued treatment due to adverse reactions2
Treat the progression of Friedreich ataxia with SKYCLARYS
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References:
1. Skyclarys. Prescribing Information. Biogen; 2024. 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. doi:10.1002/ana.25934 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. doi:10.1111/jnc.12317 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. doi:10.1038/nrneurol.2009.26 5. Rummey C, Farmer JM, Lynch DR. Predictors of loss of ambulation in Friedreich’s ataxia. eClinicalMedicine. 2020;18:1-9. doi:10.1016/j.eclinm.2019.11.006 6. Rummey C, Corben LA, Delatycki MB, et al. Psychometric properties of the Friedreich Ataxia Rating Scale. Neurol Genet. 2019;5(6):371. doi:10.1212/NXG.0000000000000371 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. doi:10.1002/acn3.332 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. 2023;38(2):313-320. 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. doi:10.1002/ana.24595 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. doi:10.1212/CPJ.0000000000000421 12. Data on file. Reata Pharmaceuticals, Inc.; 2022. 13. Lynch DR, Goldsberry A, Rummey C, et al. Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data. Ann Clin Transl Neurol. 2024;11(1):4-16. doi:10.1002/acn3.51897
14. 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. doi:10.1002/cpt.1658

INDICATION

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

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
  • 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. 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 Study 1, 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

ADVERSE REACTIONS

  • Adverse reactions reported in 10% or more of patients and greater than placebo were elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, musculoskeletal pain, oropharyngeal pain, influenza, vomiting, muscle spasms, back pain, decreased appetite, rash

DRUG INTERACTIONS

  • Avoid concomitant use of SKYCLARYS with moderate or strong CYP3A4 inhibitors. If use cannot be avoided, dosage modifications are recommended
  • Avoid concomitant use of SKYCLARYS with moderate or strong CYP3A inducers
  • Refer to the prescribing information for dosing instructions for concomitant use of CYP3A4 and CYP2C8 substrates and monitor for lack of efficacy of the concomitant treatment
  • Advise patients to avoid concomitant use with combined hormonal contraceptives, implants, and progestin only pills

SPECIFIC POPULATIONS

Pregnancy

  • There are no adequate data on the development risks associated with the use of SKYCLARYS in pregnant women

Lactation

  • There are no data on the presence of omaveloxolone or its metabolites in human milk. 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

Hepatic Impairment

  • Avoid treatment with SKYCLARYS in patients with severe hepatic impairment, including those who develop severe hepatic impairment
  • Reduced dosage in patients with moderate hepatic impairment with close monitoring for adverse reactions is recommended

Please see full Prescribing Information.

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©2024 Biogen. All rights reserved. SKY-US-0219 v3 07/2024

©2024 Biogen. All rights reserved. SKY-US-0220 v3 07/2024