Warnings and Precautions Immunosuppression and Increased Risk of Infection (5.2)                                     6/2024

 JAYTHARI is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 5 years of age and older.

JAYTHARI is contraindicated in patients with known hypersensitivity to deflazacort or to any of the inactive ingredients. Instances of hypersensitivity, including anaphylaxis, have occurred in patients receiving corticosteroid therapy

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

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 JAYTHARI may be reduced temporarily, or alternate day treatment may be introduced.

The active ingredient in JAYTHARI is deflazacort (a corticosteroid). Corticosteroids are adrenocortical steroids, both naturally occurring and synthetic. The molecular formula for deflazacort is C

Deflazacort is a white to pale yellow crystalline powder and has a molecular weight of 441.5. Deflazacort is freely soluble in acetic acid and dichloromethane and sparingly soluble in methanol and acetone.

JAYTHARI tablets for oral administration is available as an immediate-release tablet in strengths of 6, 18, 30 and 36 mg. Each tablet contains deflazacort and the following inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and pregelatinized starch.

The effectiveness of deflazacort for the treatment of DMD was established in Study 1, a multicenter, randomized, double-blind, placebo-controlled, 52-week study conducted in the US and Canada. The study population consisted of 196 male pediatric patients 5 to 15 years of age with documented mutation of the dystrophin gene, onset of weakness before 5 years of age, and serum creatinine kinase activity at least 10 times the upper limit of normal (ULN) at some stage in their illness. Patients were randomized to therapy with deflazacort (0.9 mg/kg/day or 1.2 mg/kg/day), an active comparator, or placebo. A comparison to placebo was made after 12 weeks of treatment. After 12 weeks, placebo patients were re-randomized to receive either deflazacort or the active comparator; all patients continued treatment for an additional 40 weeks. Baseline characteristics were comparable between the treatment arms.

In Study 1, efficacy was evaluated by assessing the change between Baseline and Week 12 in average strength of 18 muscle groups. Individual muscle strength was graded using a modified Medical Research Council (MRC) 11-point scale, with higher scores representing greater strength.

The change in average muscle strength score between Baseline and Week 12 was significantly greater for the deflazacort 0.9 mg/kg/day dose group than for the placebo group (see Table 2).

Compared with the deflazacort 0.9 mg/kg/day group, the deflazacort 1.2 mg/kg/day group demonstrated a small additional benefit compared to placebo at Week 12 but had a greater incidence of adverse reactions. Therefore, use of a 1.2 mg/kg/day dosage of deflazacort is not recommended

Although not a pre-specified statistical analysis, compared with placebo, the deflazacort 0.9 mg/kg/day dose group demonstrated at Week 52 the persistence of the treatment effect observed at Week 12 and the small advantage of the 1.2 mg/kg/day dose that was observed at Week 12 was no longer present. Also not statistically controlled for multiple comparisons, results on several timed measures of patient function (i.e., time to stand from supine, time to climb 4 stairs, and time to walk or run 30 feet) numerically favored deflazacort 0.9 mg/kg/day at Week 12, in comparison with placebo.

An additional randomized, double-blind, placebo-controlled, 104-week clinical trial evaluated deflazacort in comparison to placebo (Study 2). The study population consisted of 29 male children 6 to 12 years of age with a DMD diagnosis confirmed by the documented presence of abnormal dystrophin or a confirmed mutation of the dystrophin gene. The results of the analysis of the primary endpoint of average muscle strength scores in Study 2 (graded on a 0 to 5 scale) at 2 years were not statistically significant, possibly because of a limited number of patients remaining in the placebo arm (subjects were discontinued from the trial when they lost ambulation). Although not statistically controlled for multiple comparisons, average muscle strength scores at Months 6 and 12, as well as the average time to loss of ambulation, numerically favored deflazacort in comparison with placebo.

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

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

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

Advise patients and/or caregivers about the risk of osteoporosis with prolonged use of JAYTHARI, which can predispose the patient to vertebral and long bone fractures

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

Advise patients and/or caregivers to bring immunizations up-to-date according to immunization guidelines prior to starting therapy with JAYTHARI. Live-attenuated or live vaccines should be administered at least 4 to 6 weeks prior to starting JAYTHARI. Inform patients and/or caregivers that they may receive concurrent vaccinations with use of JAYTHARI, except for live-attenuated or live vaccines.

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

Certain medications can cause an interaction with JAYTHARI. 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.

Piacenza, Italy, 29016

Pennington, NJ 08534

Rev.: 10/2024

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