Deflazacort Improves Muscle Strength, Functional Outcomes in Duchenne Muscular Dystrophy

Both deflazacort groups demonstrated numerical improvements in functional measures from weeks 12 to 52 compared with prednisone, with statistically significant improvements noted in time to climb 4 stairs from baseline to 52 weeks in both deflazacort groups (P = .0461, P = .0012) compared with prednisone. Secondary end points for pulmonary function saw a significant benefit for deflazacort 1.2 mg/kg/d over prednisone for change in forced vital capacity from week 12 to 52.

When evaluating adverse events, researchers noted that there was no difference between deflazacort and placebo when comparing increase in weight at 12 weeks, while those receiving prednisone experienced a significant increase in weight (weight: LS mean 3.23 vs 1.23, P = .0459, 95% CI 0.03-3.97; BMI: LS means 1.47 vs 0.16, P = .0041, 95% CI 0.35-2.29). At 52 weeks, those treated with deflazacort had significantly smaller increases in weight and BMI compared with those treated with prednisone.

“Weight gain has implications on the loss of patient ambulation due to increased mechanical load on already impaired muscles,” the authors wrote. “In the current trial, more participants discontinued treatment due to weight gain with prednisone than deflazacort…”

Additionally, more adverse events were associated with treatment with prednisone compared with deflazacort, including Cushingoid appearance (69.4%), erythema (41.8%), and hirsutism (39.3%). Psychiatric adverse events—including abnormal behavior, aggression, irritability, and mood swings—were more common in the prednisone group than the deflazacort groups. Among those treated with deflazacort, those in the 1.2 mg/kg/d group experienced more adverse events than those in the 0.9 mg/kg/d group.

Ultimately, 0.9 mg/kg/d was submitted as the recommended dosage of deflazacort to the FDA. A decision is expected in February 2017.

Disclosures: This study was supported by Nordic Merrell Dow and the Muscular Dystrophy Association (MDA). Dr Griggs is a consultant for Sarepta Therapeutics, Bamboo Therapeutics, Marathon Pharmaceuticals, LLC, and PTC Therapeutics, and received support from the NIH, MDA, and PPMD  for studies on corticosteroids in DMD. Dr Mendell has served as a principal investigator on studies supported by Sarepta Therapeutics and aveXis Inc. Dr Cwik is an employee of the MDA. Dr Dubow and Dr Meyer are employees of Marathon Pharmaceuticals, LLC, and hold stock options.

References

1. Griggs RC, Miller JP, Greenberg CR, et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology. 2016;87:1-9. doi:10.1212/WNL.0000000000003217.
2. Marathon Pharmaceuticals announces Neurology publication of pivotal phase 3 data for deflazacort for Duchenne muscular dystrophy [press release]. Northbrook, IL; Marathon Pharmaceuticals, LLC: August 30, 2016.