Drug Information

Drug Interaction:

ACE inhibitors, anti-hypertensives, and diuretics, antacids, aspirin, barbiturates, ketoconazole, coumarins, rotonavir, and oral contraceptives

Indication:

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

EMFLAZA™ safely and effectively. See full prescribing information for EMFLAZA. EMFLAZA (deflazacort) tablets, for oral use EMFLAZA (deflazacort) oral suspension

Initial U.S. Approval: 2017

INDICATIONS AND USAGE

EMFLAZA is a corticosteroid indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 5 years of age and older

DOSAGE AND ADMINISTRATION

? The recommended once-daily dosage is approximately 0.9 mg/kg/day administered orally

? Discontinue gradually when administered for more than a few days

DOSAGE FORMS AND STRENGTHS

? Tablets: 6 mg, 18 mg, 30 mg, and 36 mg

? Oral Suspension: 22.75 mg/mL

U.S. FDA APPROVED DRUGS DURING 2017

Sr.No- 3

Name of the Drug- EMFLAZA

Active Ingredient- Deflazacort Pharmacological Classification-

To treat patients age 5 years and older with Duchenne muscular

dystrophy ( DMD)

Date of Approval- 02-09-2017

(Ref- FDA approved List 2017)

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration Silver Spring MD 20993

NDA 208684 NDA 208685

NDA APPROVAL

Marathon Pharmaceuticals, LLC

Attention: Matthew A. Lee,

PharmD Director, Regulatory Affairs

1033 Skokie Boulevard, Suite 600 Northbrook, IL 60062

Dear Dr. Lee:

Please refer to your New Drug Applications (NDAs) dated June 9, 2016,

received June 9 2016, and your amendments, submitted pursuant

to section 505(b)(2) of the Federal Food, Drug, and

Cosmetic Act (FDCA) for Emflaza (deflazacort) oral tablets 6, 18, 30, and 36 mg

and oral suspension 22.75 mg/mL.

These new drug applications provide for the use of Emflaza (deflazacort) oral tablets,

and oral suspension for the treatment of Duchenne Muscular Dystrophy

in patients 5 years of age and older.

We have completed our review of these applications, as amended.

They are approved, effective on the date of this letter, for use as recommended

in the enclosed agreed-upon labeling text.

CONTENT OF LABELING

As soon as possible, but no later than 14 days from the date of this letter,

submit the content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL)

format using the FDA automated drug registration and listing system (eLIST),

as described at

http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.

Content of labeling must be identical to the enclosed labeling

(text for the package insert, instructions for use). Information on submitting

SPL files using eLIST may be found in the guidance for industry SPL

Standard for Content of Labeling Technical Qs and As, available at

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation

/Guidances/U CM072392.pdf.

The SPL will be accessible via publicly available labeling repositories.

CARTON AND IMMEDIATE CONTAINER LABELS

Submit final printed carton and immediate container labels that are identical

to the carton and immediate container labels submitted on November 16, 2016,

as soon as they are available, but

Reference ID:

Finally, we have determined that only a clinical trial (rather than a nonclinical

or observational study) will be sufficient to identify an unexpected serious

risk of QT prolongation.

Therefore, based on appropriate scientific data, FDA has determined that you

are required to conduct the following:

3165-7 A clinical trial to assess the risk of QT prolongation with deflazacort

to exclude mean QTc effects greater than 20ms.

The timetable you submitted on February 8, 2017, states that you will conduct

this trial according to the following schedule:

Final Protocol Submission: 07/2017

Trial Completion: 09/2019

Final Report Submission: 04/2020

Please allow for adequate time for Agency review and comment on each

of the protocols, and for agreement on the protocols, prior to the

final protocol submission dates.

Submit the protocol(s) to your IND 119258 with a cross-reference letter

to NDA 208684 and NDA 208685. Submit all final report(s) to your NDAs.

Prominently identify the submission with the following wording in bold

capital letters at the top of the first page of the submission, as appropriate:

Required Postmarketing Protocol Under 505(o),

Required Postmarketing Final Report Under 505(o)

Required Postmarketing Correspondence Under 505(o).

Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically

on the status of any study or clinical trial required under this section.

This section also requires you to periodically report to FDA on the status

of any study or clinical trial otherwise undertaken to investigate a safety issue

Section 506B of the FDCA, as well as 21 CFR 314.81(b)(2)(vii),

requires you to report annually on the status of any postmarketing

commitments or required studies or clinical trials.

FDA will consider the submission of your annual report under section

506B and 21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting

requirement under section 505(o)(3)(E)(ii) provided that you include

the elements listed in 505(o) and 21 CFR 314.81(b)(2)(vii).

We remind you that to comply with 505(o), your annual report must also

include a report on the status of any study or clinical trial otherwise

undertaken to investigate a safety issue.

Failure to submit an annual report for studies or clinical trials required

under 505(o) on the date required will be considered a violation of

FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.

Adverse Reaction:

Increased susceptibilty to opportunistic infections with suppression of clinical symptoms and signs, gastrointestinal disturbances, osteoporosis, neuropsychaitric events, such as headache, vertigo, psycholgical dependence, hypmania, or depression, skin atrophy, fluid and electrolyte disturbances, glacoma and acne.

Contra-Indications:

Systemic infection, patients receiving live virus immunizatiion and hypersensitivity to deflazacort or any ingriedents in the formulation.

Dosages/ Overdosage Etc:

Severe Asthma Rheumatoid artheritis Inflammatory skin disorders

Dosage-

Acute disorders

upto 120mg daily

Maintenance - 3-18mg daily, titrated to lowest effective dose

Children- 0.25 - 1.5mg /kg daily or on alternate days

Patient Information:

PATIENT COUNSELING INFORMATION

Advise the patients and/or caregivers to read the FDA-approved patient labeling if EMFLAZA Oral Suspension is prescribed (Instructions for Use). Administration

Warn patients and/or caregivers to not stop taking EMFLAZA abruptly or without first checking with their healthcare providers as there may be a need for gradual dose reduction to decrease the risk of adrenal insufficiency

EMFLAZA may be taken with or without food.

Tablets

EMFLAZA Tablets may be taken whole or crushed and taken immediately after mixing with applesauce. Oral Suspension

EMFLAZA Oral Suspension must be shaken well prior to measuring out each dose with the enclosed oral dispenser.

The EMFLAZA Oral Suspension dose may be placed in 3-4 ounces of juice or milk, mixed thoroughly, and immediately administered. Do not take with grapefruit juice.

Discard any unused EMFLAZA Oral Suspension remaining after 1 month of first opening the bottle.

Increased Risk of Infection- Tell patients and/or caregivers to inform their healthcare provider if the patient has had recent or ongoing infections or if they have recently received a vaccine.

Medical advice should be sought immediately if the patient develops fever or other signs of infection.

Patients and/or caregivers should be made aware that some infections can potentially be severe and fatal. Warn patients who are on corticosteroids to avoid exposure to chickenpox or measles and to alert their healthcare provider immediately if they are exposed

Alterations in Cardiovascular/Renal Function- Inform patients and/or caregivers that EMFLAZA can cause an increase in blood pressure and water retention. If this occurs, dietary salt restriction and potassium supplementation may be needed

Behavioral and Mood Disturbances- Advise patients and/or caregivers about the potential for severe behavioral and mood changes with EMFLAZA and encourage them to seek medical attention if psychiatric symptoms develop

Decreases in Bone Mineral Density- Advise patients and/or caregivers about the risk of osteoporosis with prolonged use of EMFLAZA, which can predispose the patient to vertebral and long bone fractures

Ophthalmic Effects- Inform patients and/or caregivers that EMFLAZA may cause cataracts or glaucoma and advise monitoring if corticosteroid therapy is continued for more than 6 weeks

Vaccination- Advise patients and/or caregivers that the administration of live or live attenuated vaccines are not recommended. Inform them that killed or inactivated vaccines may be administered, but the responses cannot be predicted

Serious Skin Rashes- Instruct patients and/or caregivers to seek medical attention at the first sign of a rash

Drug Interactions- Certain medications can cause an interaction with EMFLAZA. Advise patients and/or caregivers to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines (such as insulin, aspirin or other NSAIDS), dietary supplements, and herbal products. Inform patients and/or caregivers that alternate therapy, dosage adjustment, and/or special test(s) may be needed during the treatment.

Manufactured for: Marathon Pharmaceuticals, LLC Northbrook, IL, 60062 U.S.A. EMFLAZA Oral Suspension made in Spain PC####X Feb 2017 EMFLAZATM is a trademark of Marathon Pharmaceuticals, LLC.

Pharmacology/ Pharmacokinetics:

Pharmacology

Deflazacort is a new glucocorticoid with lesser side-effects. It is a synthetic heterocyclic oxazoline derivative of prednisolone both anti-inflammatory and immunosuppressive activities.

Pharmacokinetics

Deflacort is well absorbed after oral admin. and immediately gets converted to pharmacogically active alcohol metabolite 21-desacetyl deflazcort ( D- 21 OH ) by plasma esterase It reaches peak plasma concentrations in about 1.5 to 2 hours.

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary- Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Animal reproduction studies have not been conducted with deflazacort.

2.Lactation Risk Summary- Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EMFLAZA and any potential adverse effects on the breastfed infant from EMFLAZA. There are no data on the effects on milk production.

3. Pediatric Use- The safety and effectiveness of EMFLAZA for the treatment of DMD have been established in patients 5 years of age and older. Use of EMFLAZA in pediatric patients is supported by a multicenter, randomized, double-blind, placebo- and active-controlled study in 196 males

Safety and effectiveness of EMFLAZA have not been established in pediatric patients less than 5 years of age.

EMFLAZA Oral Suspension contains benzyl alcohol and is not approved for use in pediatric patients less than 5 years of age.

4. Geriatric Use- DMD is largely a disease of children and young adults; therefore, there is no geriatric experience with EMFLAZA.

5. Renal Impairment- No dose adjustment is required in patients with mild, moderate or severe renal impairment [see Clinical Pharmacology (12.3)].

6.Hepatic Impairment- No dose adjustment is required in patients with mild or moderate hepatic impairment.There is no clinical experience in patients with severe hepatic impairment, and a dosing recommendation can not be provided for patients with severe hepatic impairment.

OVERDOSAGE

Treatment of acute overdosage is by immediate gastric lavage or emesis followed by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of EMFLAZA may be reduced temporarily, or alternate day treatment may be introduced.

3/17. Deflazacort- (EMFLAZA)-@- (Feb 2017)- to treat patients age 5 years and older with Duchenne muscular dystrophy(DMD)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation