By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved an oral corticosteroid to treat Duchenne muscular dystrophy (DMD) in patients ≥ 5 years of age. This follows the approval of eteplirsen, which is indicated for the treatment of DMD in patients who have confirmed mutation of the DMD gene that is amenable to exon 51 skipping. Deflazacort received fast-track designation, priority review, and orphan drug designation. It is marketed as Emflaza.
INDICATION
Deflazacort is indicated for the treatment of DMD in patients ≥ 5 years of age.1
DOSAGE
The recommended dose is 0.9 mg/kg/day.1 Deflazacort is available as 6 mg, 18 mg, 30 mg, and 36 mg tablets and as an oral suspension (22.75 mg/mL).
POTENTIAL ADVANTAGES
Deflazacort may be associated with less weight gain than prednisone. Fewer subjects discontinue treatment because of adverse events.2 The frequency of psychiatric adverse events may be lower with deflazacort.
POTENTIAL DISADVANTAGES
Common adverse events (> 10%) vs. placebo are cushingoid appearance (33% vs. 12%), weight increase (20% vs. 6%), increased appetite (14% vs. 2%), upper respiratory tract infection (12% vs. 10%), and pollakiuria (12% vs. 2%).1 Deflazacort may cause reduced growth compared to prednisone and may be associated with a higher risk of cataracts.2,3 The oral suspension contains benzyl alcohol, which is not recommended for use in pediatric patients < 5 years of age.
COMMENTS
Deflazacort is a prodrug to the active corticosteroid. The efficacy in DMD was evaluated in a randomized, double-blind, placebo-controlled, 52-week study.1,2 The population consisted of 196 male subjects 5-15 years of age with documented mutation of the dystrophin gene and onset of weakness before age 5 years and serum creatinine kinase at least 10 times above normal. Subjects were randomized to deflazacort (0.9 mg/kg/day, 1.2 mg/kg/day), prednisone (0.75 mg/kg/day), or placebo at week 12. The primary endpoint was the change from baseline in average strength of 18 muscle groups. Individual muscle strength was graded using a modified Medical Research Council 11-point scale. Mean changes from baseline were 0.15 and 0.26 for deflazacort, 0.27 for prednisone, and -0.10 for placebo. Because of higher adverse events, only the lower doses of deflazacort were approved.
CLINICAL IMPLICATIONS
DMD is an X-linked recessive neuromuscular disorder resulting in the absence or near-absence of dystrophin protein in muscle cells. This leads to muscle damage, loss of physical function, and, ultimately, premature death due to respiratory and/or cardiac failure. A Cochrane Database systematic review suggested that there is moderate quality of evidence that corticosteroid therapy in DMD improves muscle strength and function in the short term and strength up to two years.3 Limited data suggest prednisone and deflazacort possibly are equally efficacious in improving motor function.3 Deflazacort is the first FDA-approved corticosteroid for the treatment of DMD. The cost for deflazacort is $294 per 6 mg tablet compared to 20 cents for prednisone 5 mg.
REFERENCES
- Emflaza Prescribing Information. Marathon Pharmaceuticals. February 2017.
- Griggs RC, Miller JP, Greenberg CR, et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology 2016;87:2123-2131.
- Matthews E, Brassington R, Kuntzer T, et al. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev 2016 May 5;(5):CD003725. doi: 10.1002/14651858.CD003725.pub4.
Deflazacort is indicated for the treatment of Duchenne muscular dystrophy in patients ≥ 5 years of age.
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