Skyclarys

omaveloxolone · Capsule · Oral

Prescription (Rx)

Uses

1 INDICATIONS AND USAGE SKYCLARYS is indicated for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older. SKYCLARYS is indicated for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older. ( 1 )

Dosage and administration

Obtain alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, B-type natriuretic peptide (BNP), and lipid parameters prior to initiating SKYCLARYS and during treatment. ( 2.1 , 5.1 , 5.2 , 5.3 ) Recommended dosage is 150 mg (3 capsules) taken orally once daily. ( 2.2 ) Administer SKYCLARYS on an empty stomach, at least 1 hour before or 2 hours after eating. ( 2.2 ) Swallow SKYCLARYS capsules whole or open and sprinkle the entire contents of both halves of the capsule onto applesauce and mix. Do not crush or chew capsules. ( 2.2 ) Moderate and Severe Hepatic Impairment: The recommended dosage of SKYCLARYS is 100 mg once daily for patients with moderate hepatic impairment. If adverse reactions emerge, further reduce the dosage to 50 mg once daily. Avoid use in patients with severe hepatic impairment. ( 2.5 , 8.6 , 12.3 ) 2.1 Recommended Testing Before Initiating SKYCLARYS and Monitoring to Assess Safety Obtain ALT, AST, bilirubin, BNP, and lipid parameters prior to initiating SKYCLARYS and during treatment [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . 2.2 Recommended Dosage The recommended dosage of SKYCLARYS is 150 mg (3 capsules) taken orally once daily. Administer SKYCLARYS on an empty stomach, at least 1 hour before or 2 hours after eating [see Clinical Pharmacology ( 12.3 )]. Swallow SKYCLARYS capsules whole. Do not crush or chew. For patients who are unable to swallow whole capsules: SKYCLARYS capsules may be opened and the entire contents of both halves of the capsule sprinkled onto 2 tablespoons (30 mL) of applesauce [see Clinical Pharmacology ( 12.3 )] . 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. 2.3 Missed Doses 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. 2.4 Recommendations for Concomitant Use with Strong or Moderate CYP3A4 Inhibitors and Inducers The recommended dosage for concomitant use of SKYCLARYS with cytochrome P450 (CYP) 3A4 inhibitors and inducers are described in Table 1 [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )]. Table 1: Recommended Dosage of SKYCLARYS with Concomitant Use of CYP3A4 Inhibitors and Inducers Concomitant Drug Class Dosage Strong CYP3A4 inhibitor Recommended to avoid concomitant use. If coadministration cannot be avoided: Reduce the dosage of SKYCLARYS to 50 mg once daily with close monitoring for adverse reactions. If adverse reactions emerge, coadministration with strong CYP3A4 inhibitors should be discontinued. Moderate CYP3A4 inhibitor Recommended to avoid concomitant use. If coadministration cannot be avoided: Reduce the dosage of SKYCLARYS to 100 mg once daily with close monitoring for adverse reactions. If adverse reactions emerge, further reduce the dosage of SKYCLARYS to 50 mg once daily. Strong or Moderate CYP3A4 inducer Recommended to avoid concomitant use. 2.5 Recommended Dosage for Patients with Hepatic Impairment The recommended dosage for patients with hepatic impairment are described in Table 2 [see Use in Specific Populations ( 8.6 )] . Table 2: Recommended Dosage in Patients with Hepatic Impairment Impairment Classification (Child-Pugh) Dosage Severe (Child-Pugh Class C) Avoid use Moderate (Child-Pugh Class B) 100 mg once daily with close monitoring for adverse reactions Consider lowering to 50 mg once daily if adverse reactions emerge Mild (Child-Pugh Class A) 150 mg once daily

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS SKYCLARYS capsules contain 50 mg of omaveloxolone, and are supplied as opaque hard capsules having a light green body and blue cap, imprinted with “RTA 408” in white ink on the body and “50” in white ink on the cap. Capsules: 50 mg ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

Elevation of Aminotransferases: Monitor ALT, AST, and total bilirubin prior to initiation, every month for the first 3 months of treatment, and periodically thereafter. ( 2.1 , 5.1 ) Elevation of B-type Natriuretic Peptide (BNP): Advise patients of signs and symptoms of fluid overload. ( 2.1 , 5.2 ) Lipid Abnormalities: Monitor cholesterol periodically during treatment. ( 2.1 , 5.3 ) 5.1 Elevation of Aminotransferases Treatment with SKYCLARYS can cause an elevation in hepatic transaminases (ALT and AST). In Study 1 [see Clinical Studies ( 14 )] , 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 in Study 1. 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 Study 1. 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 [see Adverse Reactions ( 6.1 ) and Use in Specific Populations ( 8.6 )]. 5.2 Elevation of B-Type Natriuretic Peptide Treatment with SKYCLARYS can cause an increase in BNP, a marker of cardiac function. In Study 1, a total of 14% of patients treated with SKYCLARYS had an increase from baseline in BNP and a BNP 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's ataxia. Patients were excluded from Study 1 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's ataxia [see Adverse Reactions ( 6.1 )]. Whether the elevations in BNP in Study 1 are related to SKYCLARYS or cardiac disease associated with Friedreich's 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. 5.3 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.

Side effects

The following clinically significant adverse reactions are described in greater detail in other labeling sections: Elevation of aminotransferases [see Warnings and Precautions ( 5.1 )] Elevation of BNP [see Warnings and Precautions ( 5.2 )] Lipid abnormalities [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (incidence ≥20% and greater than placebo) are elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-844-987-3224- or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of SKYCLARYS 150 mg once daily has been evaluated in 165 patients with Friedreich's ataxia, including 137 patients exposed for at least 48 weeks, and 125 patients exposed for at least 96 weeks. The most common adverse reactions in Study 1 (≥20% and greater than placebo) were elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain. Table 3 shows the adverse reactions that occurred in 10% or more of patients treated with SKYCLARYS and greater than placebo. Table 3: Adverse Reactions Reported in 10% or More of Patients Treated with SKYCLARYS and Greater than Placebo (Study 1) Adverse Reactions SKYCLARYS 150 mg (N = 51) % Placebo (N = 52) % Elevated liver enzymes (AST/ALT) 37 2 Headache 37 25 Nausea 33 13 Abdominal pain 29 6 Fatigue 24 14 Diarrhea 20 10 Musculoskeletal pain 20 15 Oropharyngeal pain 18 6 Influenza 16 6 Vomiting 16 12 Muscle spasms 14 6 Back pain 13 8 Decreased appetite 12 4 Rash 10 4 Laboratory Abnormalities In addition to elevated liver enzymes, additional laboratory abnormalities include elevation of BNP and lipid abnormalities [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )]. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of SKYCLARYS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: hypersensitivity (urticaria, rash)

Drug interactions

Moderate or Strong CYP3A4 Inhibitors: Avoid concomitant use. Consider SKYCLARYS dosage reduction with monitoring if use is unavoidable. ( 2.4 , 7.1 ) Moderate or Strong CYP3A4 Inducers: Avoid concomitant use. ( 7.1 ) 7.1 Effect of Other Drugs on SKYCLARYS CYP3A4 Inhibitors Omaveloxolone is a CYP3A4 substrate. Concomitant use of SKYCLARYS with moderate or strong CYP3A4 inhibitors is expected to result in clinically significant increased exposure of omaveloxolone [see Clinical Pharmacology ( 12.3 )], which may increase the risk of adverse reactions. Avoid concomitant use of SKYCLARYS with moderate or strong CYP3A4 inhibitors. If use cannot be avoided, dosage modifications are recommended [see Dosage and Administration ( 2.4 )]. CYP3A4 Inducers Omaveloxolone is a CYP3A4 substrate. Concomitant use of SKYCLARYS with moderate or strong CYP3A4 inducers is expected to result in clinically significant decreased exposure of omaveloxolone [see Clinical Pharmacology ( 12.3 )] , which may reduce the effectiveness of SKYCLARYS. Avoid concomitant use of SKYCLARYS with moderate or strong CYP3A4 inducers. 7.2 Effect of SKYCLARYS on Other Drugs CYP3A4 and CYP2C8 Substrates Omaveloxolone is a weak inducer of CYP3A4 and CYP2C8. Concomitant use with SKYCLARYS can reduce the exposure of CYP3A4 and CYP2C8 substrates which may reduce the activity of these substrates [see Clinical Pharmacology ( 12.3 )] . Refer to the prescribing information of substrates of CYP3A4 and CYP2C8 for dosing instructions if used concomitantly with SKYCLARYS and monitor for lack of efficacy of the concomitant treatment. Hormonal Contraceptives Omaveloxolone is a weak CYP3A4 inducer [see Clinical Pharmacology ( 12.3 )] . Concomitant use with SKYCLARYS may reduce the efficacy of hormonal contraceptives. Advise patients to avoid concomitant use with combined hormonal contraceptives (e.g., pill, patch, ring), implants, and progestin only pills [see Use in Specific Populations ( 8.3 )] .

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SKYCLARYS during pregnancy. Healthcare providers are encouraged to enroll pregnant patients, or pregnant women may register themselves in the program by calling 1-866-609-1785 or by sending an email to SkyclarysPregnancySurveillance@ppd.com. Risk Summary There are no adequate data on the developmental risks associated with the use of SKYCLARYS in pregnant women. In animal studies, administration of omaveloxolone during pregnancy or throughout pregnancy and lactation produced evidence of developmental toxicity (embryofetal mortality and growth impairment, and mortality, growth impairment, and neurobehavioral deficits in offspring) at plasma exposures similar to or less than exposures in humans (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of omaveloxolone (0, 1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in no adverse effects on embryofetal development; however, in a dose range-finding study, oral administration of omaveloxolone at doses up to 30 mg/kg/day to pregnant rats throughout organogenesis produced increases in post-implantation loss and resorptions, resulting in a decrease in viable fetuses, and reduced fetal weight at the highest dose tested. At the highest dose tested in the pivotal study (10 mg/kg/day), plasma exposure (AUC) was approximately 5 times that in humans at the recommended human dose (RHD) of 150 mg/day. Oral administration of omaveloxolone (0, 3, 10, or 30 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality and skeletal variations and reduced fetal weight at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose for adverse effects on embryofetal development (10 mg/kg/day), plasma exposure was less than that in humans at the RHD. Oral administration of omaveloxolone (0, 1, 3, or 10 mg/kg/day) to rats throughout pregnancy and lactation resulted in an increase in stillbirths and impaired neurobehavioral function (increased locomotor activity and learning and memory deficits) in offspring at all doses, reduced body weight in offspring at all but the lowest dose tested, and delayed sexual maturation (males), increased postnatal mortality, and impaired reproductive performance in offspring at the highest dose tested. A no-effect dose for adverse effects on pre- and postnatal development was not identified. Plasma exposure (AUC) at the lowest dose tested was less than that in humans at the RHD. 8.2 Lactation Risk Summary 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. Omaveloxolone was excreted in the milk of lactating rats following oral administration. 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. 8.3 Females and Males of Reproductive Potential SKYCLARYS may decrease the efficacy of hormonal contraceptives [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )] . Advise patients to avoid concomitant use with combined hormonal contraceptives (e.g., pill, patch, ring), implants, and progestin only pills. Counsel females using hormonal contraceptives 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. 8.4 Pediatric Use The safety and effectiveness of SKYCLARYS for the treatment of Friedreich's ataxia have been established in pediatric patients aged 16 years and older. Use of SKYCLARYS for this indication is supported by evidence from one adequate and well-controlled study (Study 1) in adults and in pediatric patients aged 16 years and older [see Clinical Studies ( 14 )] . Safety and effectiveness of SKYCLARYS have not been established in pediatric patients less than 16 years of age. 8.5 Geriatric Use Clinical studies of SKYCLARYS in Friedreich's ataxia did not include patients aged 65 and over. No data are available to determine whether they respond differently than younger adult patients. 8.6 Hepatic Impairment Omaveloxolone plasma exposure is increased in patients with moderate or severe hepatic impairment (Child-Pugh Class B and C) [see Clinical Pharmacology ( 12.3 )] . Avoid treatment with SKYCLARYS in patients with severe hepatic impairment, including those who develop severe hepatic impairment. If hepatic function improves to moderate impairment, mild impairment, or normal function, initiation of SKYCLARYS treatment at the approved recommended dosage may be considered. For patients with moderate hepatic impairment, a reduced dosage is recommended with close monitoring for adverse reactions [see Dosage and Administration ( 2.5 )] . For patients with mild hepatic impairment (Child-Pugh Class A), no dose adjustments are recommended.

Pregnancy

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SKYCLARYS during pregnancy. Healthcare providers are encouraged to enroll pregnant patients, or pregnant women may register themselves in the program by calling 1-866-609-1785 or by sending an email to SkyclarysPregnancySurveillance@ppd.com. Risk Summary There are no adequate data on the developmental risks associated with the use of SKYCLARYS in pregnant women. In animal studies, administration of omaveloxolone during pregnancy or throughout pregnancy and lactation produced evidence of developmental toxicity (embryofetal mortality and growth impairment, and mortality, growth impairment, and neurobehavioral deficits in offspring) at plasma exposures similar to or less than exposures in humans (see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of omaveloxolone (0, 1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in no adverse effects on embryofetal development; however, in a dose range-finding study, oral administration of omaveloxolone at doses up to 30 mg/kg/day to pregnant rats throughout organogenesis produced increases in post-implantation loss and resorptions, resulting in a decrease in viable fetuses, and reduced fetal weight at the highest dose tested. At the highest dose tested in the pivotal study (10 mg/kg/day), plasma exposure (AUC) was approximately 5 times that in humans at the recommended human dose (RHD) of 150 mg/day. Oral administration of omaveloxolone (0, 3, 10, or 30 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality and skeletal variations and reduced fetal weight at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose for adverse effects on embryofetal development (10 mg/kg/day), plasma exposure was less than that in humans at the RHD. Oral administration of omaveloxolone (0, 1, 3, or 10 mg/kg/day) to rats throughout pregnancy and lactation resulted in an increase in stillbirths and impaired neurobehavioral function (increased locomotor activity and learning and memory deficits) in offspring at all doses, reduced body weight in offspring at all but the lowest dose tested, and delayed sexual maturation (males), increased postnatal mortality, and impaired reproductive performance in offspring at the highest dose tested. A no-effect dose for adverse effects on pre- and postnatal development was not identified. Plasma exposure (AUC) at the lowest dose tested was less than that in humans at the RHD.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of SKYCLARYS for the treatment of Friedreich's ataxia have been established in pediatric patients aged 16 years and older. Use of SKYCLARYS for this indication is supported by evidence from one adequate and well-controlled study (Study 1) in adults and in pediatric patients aged 16 years and older [see Clinical Studies ( 14 )] . Safety and effectiveness of SKYCLARYS have not been established in pediatric patients less than 16 years of age.

Geriatric use

8.5 Geriatric Use Clinical studies of SKYCLARYS in Friedreich's ataxia did not include patients aged 65 and over. No data are available to determine whether they respond differently than younger adult patients.

Description

11 DESCRIPTION SKYCLARYS contains omaveloxolone in immediate release capsules for oral administration available in a 50 mg strength. The chemical name of omaveloxolone is N-(2-cyano-3,12-dioxo-28-noroleana-1,9(11)-dien-17-yl)-2,2-difluoro-propanamide. Omaveloxolone is a white to off-white amorphous solid. The molecular formula is C 33 H 44 F 2 N 2 O 3 . Molecular weight is 554.72 g/mol. The chemical structure is: Omaveloxolone has a pKa of 7.26 and is practically insoluble in water across the physiological pH range. Capsule contents include the following inactive ingredients: croscarmellose sodium, magnesium stearate, pregelatinized starch, and silicified microcrystalline cellulose. The hard capsule shells contain FD&C Blue #1, ferric oxide yellow, hypromellose, titanium dioxide, and white ink. Chemical Structure

Mechanism of action

12.1 Mechanism of Action The precise mechanism by which omaveloxolone exerts its therapeutic effect in patients with Friedreich's ataxia is unknown. Omaveloxolone has been shown to activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in vitro and in vivo in animals and humans. The Nrf2 pathway is involved in the cellular response to oxidative stress.

How supplied

16.1 How Supplied SKYCLARYS (omaveloxolone) capsules, 50 mg, are supplied as opaque, hard capsules having a light green body and blue cap imprinted with “RTA 408” in white ink on the body and “50” in white ink on the cap. SKYCLARYS is supplied in high density polyethylene bottles that contain 90 capsules, with a foil induction seal and child-resistant closure (NDC 64406-250-90). 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. 16.1 How Supplied SKYCLARYS (omaveloxolone) capsules, 50 mg, are supplied as opaque, hard capsules having a light green body and blue cap imprinted with “RTA 408” in white ink on the body and “50” in white ink on the cap. SKYCLARYS is supplied in high density polyethylene bottles that contain 90 capsules, with a foil induction seal and child-resistant closure (NDC 64406-250-90).

Storage

16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Elevation of Aminotransferases Inform patients that elevation in aminotransferases have occurred in patients treated with SKYCLARYS. Liver function tests will be performed prior to initiating SKYCLARYS, every month for the first 3 months of treatment, and periodically thereafter as needed [see Warnings and Precautions ( 5.1 )]. Fluid Overload Inform patients that elevations in BNP, a marker of cardiac function, have occurred in patients treated with SKYCLARYS. BNP will be performed prior to initiating SKYCLARYS and if signs and symptoms of fluid overload occur, such as sudden weight gain, peripheral edema, palpitations, and shortness of breath. Advise patients to contact their healthcare provider if signs and symptoms of fluid overload develop [see Warnings and Precautions ( 5.2 )]. Lipid Abnormalities Inform patients that treatment with SKYCLARYS has been associated with increases in LDL cholesterol and decreases in HDL cholesterol. Cholesterol will be assessed prior to starting SKYCLARYS and monitored periodically during treatment [see Warnings and Precautions ( 5.3 )]. Drug Interactions Advise patients to discuss all medications they are taking, including other prescription medications, non-prescription medications, or herbal products (e.g., St. John's Wort) with their healthcare provider [see Drug Interactions ( 7 )]. Pregnancy Advise women to notify their healthcare provider if they become pregnant or intend to become pregnant during SKYCLARYS therapy. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SKYCLARYS during pregnancy [see Use in Specific Populations ( 8.1 )]. Females of Reproductive Potential Counsel females using hormonal contraceptives 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 [see Drug Interactions ( 7.2 ) and Use in Specific Populations ( 8.3 )]. Administration Advise patients to take SKYCLARYS on an empty stomach, at least 1 hour before or 2 hours after eating [see Dosage and Administration ( 2.2 )]. Advise patients to swallow SKYCLARYS capsules whole or to open the capsules and sprinkle the entire contents of both halves onto 2 tablespoons (30 mL) of applesauce, then stir the mixture. If sprinkled, advise patients to swallow the drug/applesauce mixture immediately and not to store for future use. Do not crush or chew the capsules. Inform patients that the contents of the SKYCLARYS capsules should not be mixed with milk or orange juice. Advise patients to not administer SKYCLARYS by an enteral feeding tube [see Dosage and Administration ( 2.2 )] . Advise patients that if a dose of SKYCLARYS is missed to not to double their dose or take more than the prescribed dose [see Dosage and Administration ( 2.3 )]. Advise patients to avoid grapefruit juice and grapefruit while they are taking SKYCLARYS [see Drug Interactions ( 7.1 )]. 59564-04 Manufactured for Biogen U.S. Corporation, Cambridge, MA © Biogen 2026 All rights reserved

Label text from the FDA structured product label by Biogen (revised Apr 6, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Omaveloxolone in 1 product

Skyclarys NDC products (1)

NDC	Strength & form	Labeler	Type
64406-250	Omaveloxolone 50 mg/1 Capsule	Biogen	NDA