Deflazacort in DMD
(2016)Objective
To compare the efficacy and safety of deflazacort vs prednisone vs placebo in boys with Duchenne muscular dystrophy in a definitive head-to-head trial
Study Summary
• Deflazacort caused dramatically less weight gain than prednisone (~5% vs ~18% body weight at 52 weeks, p<0.0001), establishing it as an alternative with superior weight profile
Intervention
Deflazacort 0.9 or 1.2 mg/kg/day vs prednisone 0.75 mg/kg/day vs placebo
Inclusion Criteria
Boys aged 5-15 years, weakness onset before age 5, CK >=10x ULN, confirmed dystrophin gene alteration
Study Design
Arms: Deflazacort 0.9 mg/kg/day, Deflazacort 1.2 mg/kg/day, Prednisone 0.75 mg/kg/day, Placebo
Patients per Arm: ~49 per group (196 total)
Outcome
• Weeks 12-52: DFZ 0.9 vs PRED strength difference 0.29 (p=0.044); deflazacort maintained while prednisone worsened
• Weight: PRED 18% vs DFZ 5% body weight gain at 52 weeks (p<0.0001); cataracts: DFZ 0.9 4.4% vs PRED 1.6%
Bottom Line
Both deflazacort (0.9 and 1.2 mg/kg/day) and prednisone (0.75 mg/kg/day) significantly improved muscle strength vs placebo at 12 weeks. At 52 weeks, deflazacort maintained strength while prednisone showed worsening. Deflazacort caused significantly less weight gain (5% vs 18% body weight increase, p<0.0001) than prednisone. This definitive head-to-head trial established deflazacort as an alternative with potentially superior weight profile.
Major Points
- All three active arms significantly improved average muscle strength vs placebo at 12 weeks: DFZ 0.9 (p=0.017), DFZ 1.2 (p=0.0003), Prednisone (p=0.0002)
- From weeks 12-52, deflazacort 0.9 mg/kg was superior to prednisone (strength LS mean difference 0.29, p=0.044) -- deflazacort maintained while prednisone worsened
- Weight gain dramatically less with deflazacort: 5% body weight gain vs 18% with prednisone at 52 weeks (p<0.0001)
- 4-stair climb at 52 weeks: DFZ 0.9 vs PRED p=0.046; DFZ 1.2 vs PRED p=0.001
- Cataracts more common with deflazacort 0.9 (4.4%) vs prednisone (1.6%)
- Study completed in 1995 but not published until 2016 -- 21-year publication delay
Study Design
- Study Type
- Phase III, double-blind, randomized, placebo-controlled, multicenter trial (two phases: 12-week placebo-controlled + 40-week active extension)
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 196
- Follow-up
- 52 weeks (12 weeks placebo-controlled + 40 weeks active extension)
- Centers
- 7
- Countries
- United States, Canada
Primary Outcome
Definition: Myometric muscle strength, Scott Score, timed functional tests
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| No significant improvement | Statistically significant improvement | - | <0.05 |
Limitations & Criticisms
- Study completed in 1995 but not published until 2016 -- extraordinary 21-year publication delay
- 52-week duration only; long-term comparative data needed
- Did not test alternative intermittent dosing regimens (e.g., weekend)
- 6-minute walk distance not used as outcome measure (study predated widespread adoption)
- Placebo group reassigned to active at 12 weeks, limiting long-term placebo comparison
- Marathon Pharmaceuticals submitted NDA based on this data; industry involvement in delayed publication
Citation
Griggs RC et al. Neurology. 2016 Nov 15;87(20):2123-2131. DOI: 10.1212/WNL.0000000000003217. PMID: 27566742. PMCID: PMC5109941