These Highlights Do Not Include All The Information Needed To Use Agamree ®

Risk of Adrenal Insufficiency Following Withdrawal

AGAMREE produces reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, with the potential for the development of secondary adrenal insufficiency after withdrawal. Acute adrenal insufficiency can occur if AGAMREE is withdrawn abruptly, and could be fatal. The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose and duration of therapy.

The risk of adrenal insufficiency is reduced by gradually tapering the dose when withdrawing treatment. The insufficiency may persist, however, for months after discontinuation of prolonged therapy; therefore, in any situation of stress occurring during that period of discontinuation, supplementation with a systemic corticosteroid is recommended. For patients already taking corticosteroids during times of stress, the dosage may need to be increased.

A steroid “withdrawal syndrome”, seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of corticosteroids. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or weight loss. These effects are thought to be due to the sudden change in corticosteroid concentration rather than too low corticosteroid levels.

Principal Display Panel – 100 mL Carton Label

NDC 69616-264-38

100 mL

AGAMREE ^®

(vamorolone)

Oral suspension

Rx only

40 mg/mL

For Oral Administration Only

Catalyst Pharmaceuticals, Inc.

Instructions for Use

AGAMREE ^® (ah gam' ree)

(vamorolone)

40 mg/mL oral suspension

Read this Instructions for Use before you start using AGAMREE oral suspension and each time you get a new bottle.

This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Supplies provided in the AGAMREE carton:

Important information you need to know before taking AGAMREE:

• For oral use only(take by mouth).
• Always use the oral syringes provided with your AGAMREE oral suspension to make sure you measure the right amount.
• Ask your healthcare provider or pharmacist to show you how to measure your prescribed daily dose using the oral syringe.
• Call your pharmacist if your oral syringes are lost or damaged.
• Each oral syringe can be used for 45 days. Call your pharmacist if you need more oral syringes.
• Take AGAMREE exactly as your healthcare provider tells you to take it. Do notstop taking AGAMREE suddenly without first speaking with your healthcare provider.
• AGAMREE oral suspension should be taken 1-time daily with a meal.
• Do notmix the AGAMREE oral suspension with any type of liquids before taking or giving the prescribed daily dose.
• Do notuse AGAMREE 3 months after opening the bottle. Write the date of first opening on your AGAMREE bottle when you first open it.

Storing AGAMREE

• Store the unopened bottle upright at room temperature between 68°F to 77°F (20°C to 25°C) in the original carton. After opening the bottle, store the bottle upright in a refrigerator between 36°F to 46°F (2°C to 8°C).
• Do notfreeze.
• Throw away (discard) any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

Keep AGAMREE oral suspension and all medicines out of the reach of children.

For further information call 1-833-422-8259 or go to www.YourCatalystPathways.com.

Manufactured for: Catalyst Pharmaceuticals, Inc., Coral Gables, FL 33134

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 03/2024

Treatment of acute overdosage of vamorolone is by immediate supportive and symptomatic therapy. Gastric lavage or emesis can be considered.

Patients receiving corticosteroids and concomitant therapy with neuromuscular blocking agents (e.g., pancuronium) or patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) may be at increased risk of developing acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

AGAMREE (vamorolone) oral suspension contains vamorolone, a corticosteroid. Vamorolone [17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione] is a white to off-white powder with a molecular formula of C ₂₂H ₂₈O ₄and a molecular weight of 356.46 g/mol. Its structural formula is:

Vamorolone is freely soluble in methanol and dioxane and sparingly soluble in ethanol and acetone.

AGAMREE for oral administration is available as an oral suspension in a strength of 40 mg/mL. The oral suspension contains vamorolone and the following inactive ingredients: citric acid (monohydrate), disodium phosphate, glycerin, hydrochloric acid (for pH adjustment), orange flavor, sodium benzoate, sucralose, water, and xanthan gum.

Rare instances of anaphylaxis have occurred in patients receiving corticosteroid therapy.

AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone.

AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38.

Administer all immunizations according to immunization guidelines prior to starting AGAMREE. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE. Patients on AGAMREE may receive concurrent vaccinations, except for live-attenuated or live vaccines.

The safety and effectiveness of AGAMREE for the treatment of DMD have been established in patients 2 years of age and older. Use of AGAMREE in pediatric patients is supported by a multicenter, randomized, double-blind, placebo- and active-controlled study in 121 males 4 to less than 7 years of age [see Clinical Studies ( 14)]. Use of AGAMREE in patients 2 years to less than 4 years of age and 7 to less than 18 years of age is supported by findings of efficacy and safety in patients 4 to less than 7 years of age with DMD, and by pharmacokinetic and safety data from patients 2 to 4 years of age and 7 to less than 18 years of age [see Adverse Reactions ( 6.1) and Clinical Pharmacology ( 12.3)] .

The safety and effectiveness in pediatric patients below the age of 2 years have not been established.

DMD is largely a disease of children and young adults; therefore, there is no geriatric experience with AGAMREE.

The effectiveness of AGAMREE for the treatment of Duchenne muscular dystrophy (DMD) was evaluated in a multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled, multinational 24-week study (Study 1; NCT03439670). The study randomized 121 male patients with DMD to one of the following treatment groups: AGAMREE 6 mg/kg/day (n=30), AGAMREE 2 mg/kg/day (n=30), prednisone 0.75 mg/kg/day (n=31), or placebo (n=30) for 24 weeks. After 24 weeks, patients on prednisone and placebo received either AGAMREE 6 mg/kg/day (n=29) or AGAMREE 2 mg/kg/day (n=29) for an additional 20 weeks. The study included patients 4 to less than 7 years of age at time of enrollment in the study who were corticosteroid naïve and ambulatory, with a confirmed diagnosis of DMD. At baseline, patients had a mean age of 5.4 years, 83% were Caucasian, 10% were Asian, and 96% were not Hispanic or Latino.

The primary endpoint was the change from baseline to Week 24 in Time to Stand Test (TTSTAND) velocity for AGAMREE 6 mg/kg/day compared to placebo. TTSTAND velocity is a measure of muscle function that measures the time required for the patient to stand to an erect position from a supine position (floor). The key secondary endpoints consisted of change from baseline to Week 24 in TTSTAND velocity (AGAMREE 2 mg/kg/day vs placebo), 6 Minute Walk Test (6MWT) distance (AGAMREE 6 mg/kg/day vs placebo and 2 mg/kg/day vs placebo) and Time to Run/Walk 10 meters (TTRW) velocity (AGAMREE 6 mg/kg/day vs placebo and 2 mg/kg/day vs placebo). The 6MWT measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes and TTRW measures the time that it takes a patient to run or walk 10 meters. The fixed sequential testing process was applied to the key secondary endpoints in the order listed above.

The primary endpoint and key secondary endpoints were met for the AGAMREE 6 mg/kg/day treatment group. The AGAMREE 2 mg/kg/day treatment group was statistically significant vs. placebo for TTSTAND and 6MWT, but was not statistically significant vs. placebo for TTRW. See Figure 1and Table 2for efficacy results from Week 24.

Figure 1: Least-Squares Mean Change in Time to Stand (TTSTAND) Velocity (rises/sec)

Dosage of AGAMREE must be decreased gradually if the drug has been administered for more than one week [see Warnings and Precautions ( 5.1)].

AGAMREE is contraindicated in patients with known hypersensitivity to vamorolone or to any of the inactive ingredients of AGAMREE. Instances of hypersensitivity, including anaphylaxis, have occurred in patients receiving corticosteroid therapy [see Warnings and Precautions ( 5.13)].

The following serious adverse reactions are discussed in more detail in other sections:

• Alterations in Endocrine Function [see Warnings and Precautions ( 5.1)]
• Immunosuppression and Increased Risk of Infection [see Warnings and Precautions ( 5.2)]
• Alterations in Cardiovascular/Renal Function [see Warnings and Precautions ( 5.3)]
• Gastrointestinal Perforation [see Warnings and Precautions ( 5.4)]
• Behavioral and Mood Disturbances [see Warnings and Precautions ( 5.5)]
• Effects on Bones [see Warnings and Precautions ( 5.6)]
• Ophthalmic Effects [see Warnings and Precautions ( 5.7)]
• Immunizations [see Warnings and Precautions ( 5.8)]
• Effects on Growth and Development [see Warnings and Precautions ( 5.9)]
• Myopathy [see Warnings and Precautions ( 5.10)]
• Kaposi's Sarcoma [see Warnings and Precautions ( 5.11)]
• Thromboembolic Events [see Warnings and Precautions ( 5.12)]
• Anaphylaxis [see Warnings and Precautions ( 5.13)]

• Strong CYP3A4 inhibitors: The maximum recommended daily dose is 4 mg/kg up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg. ( 2.6, 7.1)

Vamorolone produced a dose-dependent decrease in morning cortisol levels in the clinical studies. Treatment with corticosteroids is associated with a suppression of endogenous cortisol concentrations and an impairment of the hypothalamus-pituitary-adrenal (HPA) axis function. A dose-dependent increase in leukocyte counts and lymphocyte counts was observed in clinical studies with vamorolone.

The major route of elimination is by metabolism with subsequent excretion of metabolites into urine. The pharmacokinetics (PK) are linear and vamorolone exposure increases proportionally with either single (0.1 to 20 mg/kg) or multiple (0.25 to 20 mg/kg) doses. Vamorolone does not accumulate with repeated administration after once daily dosing.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi's sarcoma.

The recommended dosage of AGAMREE is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg.

Some patients may respond to a dose of 2 mg/kg daily. Doses may be titrated down to 2 mg/kg/day as needed, based on individual tolerability.

The use of corticosteroids, such as AGAMREE, may produce posterior subcapsular cataracts. Corticosteroids may also cause glaucoma with possible damage to the optic nerves, and may increase the risk of secondary ocular infections caused by bacteria, fungi, or viruses. Corticosteroids are not recommended for patients with active ocular herpes simplex. Intraocular pressure may become elevated in some patients taking corticosteroids. If treatment with AGAMREE is continued for more than 6 weeks, monitor intraocular pressure.

Moderate hepatic impairment increases vamorolone exposure [see Clinical Pharmacology ( 12.3)]. Reduce the AGAMREE dosage in patients with mild to moderate hepatic impairment [see Dosage and Administration ( 2.3)]. There is no clinical experience with AGAMREE in patients with severe hepatic impairment, and a dosing recommendation cannot be provided for patients with severe hepatic impairment.

AGAMREE is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older.

Vamorolone is a corticosteroid that acts through the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The precise mechanism by which vamorolone exerts its effect in patients with DMD is unknown.

Store the bottle upright at room temperature between 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F) in the original carton. See USP controlled room temperature.

After opening, store the bottle upright in a refrigerator 2°C to 8°C (36°F to 46°F). Do not freeze.

Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

• Alterations in Endocrine Function:Hypothalamic-pituitary-adrenal axis suppression, cushingoid features, and hyperglycemia can occur. Monitor patients for these conditions with chronic use of AGAMREE. ( 2.7, 5.1)
• Immunosuppression and Increased Risk of Infection:Increased risk of new infections, exacerbation, dissemination, or reactivation of latent infections, which can be severe and at times fatal; signs and symptoms of infections may be masked. ( 5.2)
• Alterations in Cardiovascular/Renal Function:Monitor for elevated blood pressure and monitor sodium and potassium levels in patients chronically treated with AGAMREE. ( 5.3)
• Gastrointestinal Perforation:Increased risk in patients with certain GI disorders; signs and symptoms may be masked. ( 5.4)
• Behavioral and Mood Disturbances:May include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis. ( 5.5)
• Effects on Bones:Monitor for decreases in bone mineral density with chronic use of AGAMREE. ( 5.6)
• Ophthalmic Effects:May include cataracts, infections, and glaucoma; monitor intraocular pressure in patients chronically treated with AGAMREE. ( 5.7)
• Vaccination:Do not administer live or live attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE. ( 5.8)

Observational studies have shown an increased risk of thromboembolism (including venous thromboembolism) particularly with higher cumulative doses of corticosteroids. It is unclear if risk differs by daily dose or duration of use. Use AGAMREE with caution in patients who have or may be predisposed to thromboembolic disorders.

• The recommended dosage is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. ( 2.2)
• In patients with mild to moderate hepatic impairment, the recommended dosage is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg. ( 2.3)
• Decrease dosage gradually when administered for more than one week. ( 2.7)

Oral Suspension: 40 mg/mL orange flavored white to off-white suspension

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

There is an increased risk of gastrointestinal perforation with use of corticosteroids in patients with certain gastrointestinal disorders, such as active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis. Signs of gastrointestinal perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids.

Avoid AGAMREE if there is a probability of impending perforation, abscess, or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.

Advise the patients and/or caregivers to read the FDA-approved patient labeling ( Instructions for Use).

Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including AGAMREE. Symptoms typically emerge within a few days or weeks of starting treatment and may be dose-related. These reactions may improve after either dose reduction or withdrawal, although pharmacologic treatment may be necessary.

In Study 1, psychiatric adverse reactions were reported in 21% of patients on AGAMREE 6 mg/kg, 10% of patients on AGAMREE 2 mg/kg, and 14% of patients on placebo. Psychiatric adverse reactions reported on AGAMREE resolved without requiring treatment or drug discontinuation.

In adults, psychiatric adverse reactions with corticosteroids usually involve hypomanic or manic symptoms (e.g., euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment. In children receiving corticosteroids, psychiatric adverse reactions usually involve hyperactivity symptoms (e.g., irritability, aggressive behavior, increased frequency of tantrums, and mood swings) and sleep disorder during treatment. Inform patients or caregivers of the potential for behavioral and mood changes and encourage them to seek medical attention if psychiatric symptoms develop, especially if depressed mood or suicidal ideation is suspected.

Corticosteroids, such as AGAMREE, can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients receiving AGAMREE for Cushing's syndrome, hyperglycemia, and adrenal insufficiency after AGAMREE withdrawal. In addition, patients with hypopituitarism, primary adrenal insufficiency or congenital adrenal hyperplasia, altered thyroid function, or pheochromocytoma may be at increased risk for adverse endocrine events.

Long-term use of corticosteroids, including AGAMREE, can have negative effects on growth and development in children.

Co-administration of AGAMREE with itraconazole, a strong CYP3A4 inhibitor, increases vamorolone exposure [see Clinical Pharmacology ( 12.3)] . Reduce the dosage of AGAMREE in patients when strong CYP3A4 inhibitors are used concomitantly [see Dosage and Administration ( 2.6)] . No dosage adjustments are required when AGAMREE is concomitantly administered with moderate or weak CYP3A4 inhibitors.

The recommended dosage of AGAMREE in patients with mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg [see Use in Specific Populations ( 8.6) and Clinical Pharmacology ( 12.3)] .

Doses may be titrated down based on individual tolerability.

Administer all immunizations according to immunization guidelines prior to starting AGAMREE. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE [see Warnings and Precautions ( 5.8)].

Corticosteroids, including AGAMREE, can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium.

Monitor blood pressure and assess for signs and symptoms of volume overload. Monitor serum potassium levels.

AGAMREE should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency. Literature reports suggest an association between use of corticosteroids and left free wall rupture after a recent myocardial infarction; therefore, therapy with AGAMREE should be used with great caution in these patients.

Corticosteroids, including AGAMREE, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens.

Corticosteroids can:

• reduce resistance to new infections
• exacerbate existing infections
• increase the risk of disseminated infections
• increase the risk of reactivation or exacerbation of latent infections
• mask some signs of infection

Corticosteroid-associated infections can be mild but can be severe, and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages.

Monitor for the development of infection and consider AGAMREE withdrawal or dosage reduction as needed.

Patients can be switched from oral corticosteroid treatment (such as prednisone or deflazacort) to AGAMREE without treatment interruption or period of prior corticosteroid dosage reduction to minimize the risk for adrenal insufficiency.

Patients switching after long-term treatment with oral corticosteroids should start AGAMREE at a dosage of 6 mg/kg/day.

Shake AGAMREE oral suspension well for about 30 seconds before administration.

Use only the oral syringe provided with the product. After withdrawing the appropriate dose into the oral syringe, dispense directly into the mouth.

Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

The recommended dosage of AGAMREE when administered with strong CYP3A4 inhibitors is 4 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg [see Drug Interactions ( 7.1) and Clinical Pharmacology ( 12.3)].

Doses may be titrated down based on individual tolerability.

Risk of Adrenal Insufficiency Following Withdrawal

AGAMREE produces reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, with the potential for the development of secondary adrenal insufficiency after withdrawal. Acute adrenal insufficiency can occur if AGAMREE is withdrawn abruptly, and could be fatal. The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose and duration of therapy.

The risk of adrenal insufficiency is reduced by gradually tapering the dose when withdrawing treatment. The insufficiency may persist, however, for months after discontinuation of prolonged therapy; therefore, in any situation of stress occurring during that period of discontinuation, supplementation with a systemic corticosteroid is recommended. For patients already taking corticosteroids during times of stress, the dosage may need to be increased.

A steroid “withdrawal syndrome”, seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of corticosteroids. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or weight loss. These effects are thought to be due to the sudden change in corticosteroid concentration rather than too low corticosteroid levels.

Principal Display Panel – 100 mL Carton Label

NDC 69616-264-38

100 mL

AGAMREE ^®

(vamorolone)

Oral suspension

Rx only

40 mg/mL

For Oral Administration Only

Catalyst Pharmaceuticals, Inc.

Instructions for Use

AGAMREE ^® (ah gam' ree)

(vamorolone)

40 mg/mL oral suspension

Read this Instructions for Use before you start using AGAMREE oral suspension and each time you get a new bottle.

This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Supplies provided in the AGAMREE carton:

Important information you need to know before taking AGAMREE:

• For oral use only(take by mouth).
• Always use the oral syringes provided with your AGAMREE oral suspension to make sure you measure the right amount.
• Ask your healthcare provider or pharmacist to show you how to measure your prescribed daily dose using the oral syringe.
• Call your pharmacist if your oral syringes are lost or damaged.
• Each oral syringe can be used for 45 days. Call your pharmacist if you need more oral syringes.
• Take AGAMREE exactly as your healthcare provider tells you to take it. Do notstop taking AGAMREE suddenly without first speaking with your healthcare provider.
• AGAMREE oral suspension should be taken 1-time daily with a meal.
• Do notmix the AGAMREE oral suspension with any type of liquids before taking or giving the prescribed daily dose.
• Do notuse AGAMREE 3 months after opening the bottle. Write the date of first opening on your AGAMREE bottle when you first open it.

Storing AGAMREE

• Store the unopened bottle upright at room temperature between 68°F to 77°F (20°C to 25°C) in the original carton. After opening the bottle, store the bottle upright in a refrigerator between 36°F to 46°F (2°C to 8°C).
• Do notfreeze.
• Throw away (discard) any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

Keep AGAMREE oral suspension and all medicines out of the reach of children.

For further information call 1-833-422-8259 or go to www.YourCatalystPathways.com.

Manufactured for: Catalyst Pharmaceuticals, Inc., Coral Gables, FL 33134

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 03/2024

Treatment of acute overdosage of vamorolone is by immediate supportive and symptomatic therapy. Gastric lavage or emesis can be considered.

Patients receiving corticosteroids and concomitant therapy with neuromuscular blocking agents (e.g., pancuronium) or patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) may be at increased risk of developing acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

AGAMREE (vamorolone) oral suspension contains vamorolone, a corticosteroid. Vamorolone [17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione] is a white to off-white powder with a molecular formula of C ₂₂H ₂₈O ₄and a molecular weight of 356.46 g/mol. Its structural formula is:

Vamorolone is freely soluble in methanol and dioxane and sparingly soluble in ethanol and acetone.

AGAMREE for oral administration is available as an oral suspension in a strength of 40 mg/mL. The oral suspension contains vamorolone and the following inactive ingredients: citric acid (monohydrate), disodium phosphate, glycerin, hydrochloric acid (for pH adjustment), orange flavor, sodium benzoate, sucralose, water, and xanthan gum.

Rare instances of anaphylaxis have occurred in patients receiving corticosteroid therapy.

AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone.

AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38.

Administer all immunizations according to immunization guidelines prior to starting AGAMREE. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE. Patients on AGAMREE may receive concurrent vaccinations, except for live-attenuated or live vaccines.

The safety and effectiveness of AGAMREE for the treatment of DMD have been established in patients 2 years of age and older. Use of AGAMREE in pediatric patients is supported by a multicenter, randomized, double-blind, placebo- and active-controlled study in 121 males 4 to less than 7 years of age [see Clinical Studies ( 14)]. Use of AGAMREE in patients 2 years to less than 4 years of age and 7 to less than 18 years of age is supported by findings of efficacy and safety in patients 4 to less than 7 years of age with DMD, and by pharmacokinetic and safety data from patients 2 to 4 years of age and 7 to less than 18 years of age [see Adverse Reactions ( 6.1) and Clinical Pharmacology ( 12.3)] .

The safety and effectiveness in pediatric patients below the age of 2 years have not been established.

DMD is largely a disease of children and young adults; therefore, there is no geriatric experience with AGAMREE.

The effectiveness of AGAMREE for the treatment of Duchenne muscular dystrophy (DMD) was evaluated in a multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled, multinational 24-week study (Study 1; NCT03439670). The study randomized 121 male patients with DMD to one of the following treatment groups: AGAMREE 6 mg/kg/day (n=30), AGAMREE 2 mg/kg/day (n=30), prednisone 0.75 mg/kg/day (n=31), or placebo (n=30) for 24 weeks. After 24 weeks, patients on prednisone and placebo received either AGAMREE 6 mg/kg/day (n=29) or AGAMREE 2 mg/kg/day (n=29) for an additional 20 weeks. The study included patients 4 to less than 7 years of age at time of enrollment in the study who were corticosteroid naïve and ambulatory, with a confirmed diagnosis of DMD. At baseline, patients had a mean age of 5.4 years, 83% were Caucasian, 10% were Asian, and 96% were not Hispanic or Latino.

The primary endpoint was the change from baseline to Week 24 in Time to Stand Test (TTSTAND) velocity for AGAMREE 6 mg/kg/day compared to placebo. TTSTAND velocity is a measure of muscle function that measures the time required for the patient to stand to an erect position from a supine position (floor). The key secondary endpoints consisted of change from baseline to Week 24 in TTSTAND velocity (AGAMREE 2 mg/kg/day vs placebo), 6 Minute Walk Test (6MWT) distance (AGAMREE 6 mg/kg/day vs placebo and 2 mg/kg/day vs placebo) and Time to Run/Walk 10 meters (TTRW) velocity (AGAMREE 6 mg/kg/day vs placebo and 2 mg/kg/day vs placebo). The 6MWT measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes and TTRW measures the time that it takes a patient to run or walk 10 meters. The fixed sequential testing process was applied to the key secondary endpoints in the order listed above.

The primary endpoint and key secondary endpoints were met for the AGAMREE 6 mg/kg/day treatment group. The AGAMREE 2 mg/kg/day treatment group was statistically significant vs. placebo for TTSTAND and 6MWT, but was not statistically significant vs. placebo for TTRW. See Figure 1and Table 2for efficacy results from Week 24.

Figure 1: Least-Squares Mean Change in Time to Stand (TTSTAND) Velocity (rises/sec)

Dosage of AGAMREE must be decreased gradually if the drug has been administered for more than one week [see Warnings and Precautions ( 5.1)].

AGAMREE is contraindicated in patients with known hypersensitivity to vamorolone or to any of the inactive ingredients of AGAMREE. Instances of hypersensitivity, including anaphylaxis, have occurred in patients receiving corticosteroid therapy [see Warnings and Precautions ( 5.13)].

The following serious adverse reactions are discussed in more detail in other sections:

• Alterations in Endocrine Function [see Warnings and Precautions ( 5.1)]
• Immunosuppression and Increased Risk of Infection [see Warnings and Precautions ( 5.2)]
• Alterations in Cardiovascular/Renal Function [see Warnings and Precautions ( 5.3)]
• Gastrointestinal Perforation [see Warnings and Precautions ( 5.4)]
• Behavioral and Mood Disturbances [see Warnings and Precautions ( 5.5)]
• Effects on Bones [see Warnings and Precautions ( 5.6)]
• Ophthalmic Effects [see Warnings and Precautions ( 5.7)]
• Immunizations [see Warnings and Precautions ( 5.8)]
• Effects on Growth and Development [see Warnings and Precautions ( 5.9)]
• Myopathy [see Warnings and Precautions ( 5.10)]
• Kaposi's Sarcoma [see Warnings and Precautions ( 5.11)]
• Thromboembolic Events [see Warnings and Precautions ( 5.12)]
• Anaphylaxis [see Warnings and Precautions ( 5.13)]

• Strong CYP3A4 inhibitors: The maximum recommended daily dose is 4 mg/kg up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg. ( 2.6, 7.1)

Vamorolone produced a dose-dependent decrease in morning cortisol levels in the clinical studies. Treatment with corticosteroids is associated with a suppression of endogenous cortisol concentrations and an impairment of the hypothalamus-pituitary-adrenal (HPA) axis function. A dose-dependent increase in leukocyte counts and lymphocyte counts was observed in clinical studies with vamorolone.

The major route of elimination is by metabolism with subsequent excretion of metabolites into urine. The pharmacokinetics (PK) are linear and vamorolone exposure increases proportionally with either single (0.1 to 20 mg/kg) or multiple (0.25 to 20 mg/kg) doses. Vamorolone does not accumulate with repeated administration after once daily dosing.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi's sarcoma.

The recommended dosage of AGAMREE is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg.

Some patients may respond to a dose of 2 mg/kg daily. Doses may be titrated down to 2 mg/kg/day as needed, based on individual tolerability.

The use of corticosteroids, such as AGAMREE, may produce posterior subcapsular cataracts. Corticosteroids may also cause glaucoma with possible damage to the optic nerves, and may increase the risk of secondary ocular infections caused by bacteria, fungi, or viruses. Corticosteroids are not recommended for patients with active ocular herpes simplex. Intraocular pressure may become elevated in some patients taking corticosteroids. If treatment with AGAMREE is continued for more than 6 weeks, monitor intraocular pressure.

Moderate hepatic impairment increases vamorolone exposure [see Clinical Pharmacology ( 12.3)]. Reduce the AGAMREE dosage in patients with mild to moderate hepatic impairment [see Dosage and Administration ( 2.3)]. There is no clinical experience with AGAMREE in patients with severe hepatic impairment, and a dosing recommendation cannot be provided for patients with severe hepatic impairment.

AGAMREE is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older.

Vamorolone is a corticosteroid that acts through the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The precise mechanism by which vamorolone exerts its effect in patients with DMD is unknown.

Store the bottle upright at room temperature between 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F) in the original carton. See USP controlled room temperature.

After opening, store the bottle upright in a refrigerator 2°C to 8°C (36°F to 46°F). Do not freeze.

Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

• Alterations in Endocrine Function:Hypothalamic-pituitary-adrenal axis suppression, cushingoid features, and hyperglycemia can occur. Monitor patients for these conditions with chronic use of AGAMREE. ( 2.7, 5.1)
• Immunosuppression and Increased Risk of Infection:Increased risk of new infections, exacerbation, dissemination, or reactivation of latent infections, which can be severe and at times fatal; signs and symptoms of infections may be masked. ( 5.2)
• Alterations in Cardiovascular/Renal Function:Monitor for elevated blood pressure and monitor sodium and potassium levels in patients chronically treated with AGAMREE. ( 5.3)
• Gastrointestinal Perforation:Increased risk in patients with certain GI disorders; signs and symptoms may be masked. ( 5.4)
• Behavioral and Mood Disturbances:May include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis. ( 5.5)
• Effects on Bones:Monitor for decreases in bone mineral density with chronic use of AGAMREE. ( 5.6)
• Ophthalmic Effects:May include cataracts, infections, and glaucoma; monitor intraocular pressure in patients chronically treated with AGAMREE. ( 5.7)
• Vaccination:Do not administer live or live attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE. ( 5.8)

Observational studies have shown an increased risk of thromboembolism (including venous thromboembolism) particularly with higher cumulative doses of corticosteroids. It is unclear if risk differs by daily dose or duration of use. Use AGAMREE with caution in patients who have or may be predisposed to thromboembolic disorders.

• The recommended dosage is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. ( 2.2)
• In patients with mild to moderate hepatic impairment, the recommended dosage is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg. ( 2.3)
• Decrease dosage gradually when administered for more than one week. ( 2.7)

Oral Suspension: 40 mg/mL orange flavored white to off-white suspension

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

There is an increased risk of gastrointestinal perforation with use of corticosteroids in patients with certain gastrointestinal disorders, such as active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis. Signs of gastrointestinal perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids.

Avoid AGAMREE if there is a probability of impending perforation, abscess, or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.

Advise the patients and/or caregivers to read the FDA-approved patient labeling ( Instructions for Use).

Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including AGAMREE. Symptoms typically emerge within a few days or weeks of starting treatment and may be dose-related. These reactions may improve after either dose reduction or withdrawal, although pharmacologic treatment may be necessary.

In Study 1, psychiatric adverse reactions were reported in 21% of patients on AGAMREE 6 mg/kg, 10% of patients on AGAMREE 2 mg/kg, and 14% of patients on placebo. Psychiatric adverse reactions reported on AGAMREE resolved without requiring treatment or drug discontinuation.

In adults, psychiatric adverse reactions with corticosteroids usually involve hypomanic or manic symptoms (e.g., euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment. In children receiving corticosteroids, psychiatric adverse reactions usually involve hyperactivity symptoms (e.g., irritability, aggressive behavior, increased frequency of tantrums, and mood swings) and sleep disorder during treatment. Inform patients or caregivers of the potential for behavioral and mood changes and encourage them to seek medical attention if psychiatric symptoms develop, especially if depressed mood or suicidal ideation is suspected.

Corticosteroids, such as AGAMREE, can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients receiving AGAMREE for Cushing's syndrome, hyperglycemia, and adrenal insufficiency after AGAMREE withdrawal. In addition, patients with hypopituitarism, primary adrenal insufficiency or congenital adrenal hyperplasia, altered thyroid function, or pheochromocytoma may be at increased risk for adverse endocrine events.

Long-term use of corticosteroids, including AGAMREE, can have negative effects on growth and development in children.

Co-administration of AGAMREE with itraconazole, a strong CYP3A4 inhibitor, increases vamorolone exposure [see Clinical Pharmacology ( 12.3)] . Reduce the dosage of AGAMREE in patients when strong CYP3A4 inhibitors are used concomitantly [see Dosage and Administration ( 2.6)] . No dosage adjustments are required when AGAMREE is concomitantly administered with moderate or weak CYP3A4 inhibitors.

The recommended dosage of AGAMREE in patients with mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg [see Use in Specific Populations ( 8.6) and Clinical Pharmacology ( 12.3)] .

Doses may be titrated down based on individual tolerability.

Administer all immunizations according to immunization guidelines prior to starting AGAMREE. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE [see Warnings and Precautions ( 5.8)].

Corticosteroids, including AGAMREE, can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium.

Monitor blood pressure and assess for signs and symptoms of volume overload. Monitor serum potassium levels.

AGAMREE should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency. Literature reports suggest an association between use of corticosteroids and left free wall rupture after a recent myocardial infarction; therefore, therapy with AGAMREE should be used with great caution in these patients.

Corticosteroids, including AGAMREE, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens.

Corticosteroids can:

• reduce resistance to new infections
• exacerbate existing infections
• increase the risk of disseminated infections
• increase the risk of reactivation or exacerbation of latent infections
• mask some signs of infection

Corticosteroid-associated infections can be mild but can be severe, and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages.

Monitor for the development of infection and consider AGAMREE withdrawal or dosage reduction as needed.

Patients can be switched from oral corticosteroid treatment (such as prednisone or deflazacort) to AGAMREE without treatment interruption or period of prior corticosteroid dosage reduction to minimize the risk for adrenal insufficiency.

Patients switching after long-term treatment with oral corticosteroids should start AGAMREE at a dosage of 6 mg/kg/day.

Shake AGAMREE oral suspension well for about 30 seconds before administration.

Use only the oral syringe provided with the product. After withdrawing the appropriate dose into the oral syringe, dispense directly into the mouth.

Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

The recommended dosage of AGAMREE when administered with strong CYP3A4 inhibitors is 4 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg [see Drug Interactions ( 7.1) and Clinical Pharmacology ( 12.3)].

Doses may be titrated down based on individual tolerability.