PT  - JOURNAL ARTICLE
AU  - Hoffman, Eric P.
AU  - Schwartz, Benjamin D.
AU  - Mengle-Gaw, Laurel J.
AU  - Smith, Edward C.
AU  - Castro, Diana
AU  - Mah, Jean K.
AU  - McDonald, Craig M.
AU  - Kuntz, Nancy L.
AU  - Finkel, Richard S.
AU  - Guglieri, Michela
AU  - Bushby, Katharine
AU  - Tulinius, Mar
AU  - Nevo, Yoram
AU  - Ryan, Monique M.
AU  - Webster, Richard
AU  - Smith, Andrea L.
AU  - Morgenroth, Lauren P.
AU  - Arrieta, Adrienne
AU  - Shimony, Maya
AU  - Siener, Catherine
AU  - Jaros, Mark
AU  - Shale, Phil
AU  - McCall, John M.
AU  - Nagaraju, Kanneboyina
AU  - van den Anker, John
AU  - Conklin, Laurie S.
AU  - Cnaan, Avital
AU  - Gordish-Dressman, Heather
AU  - Damsker, Jesse M.
AU  - Clemens, Paula R.
AU  - ,
TI  - Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function
AID  - 10.1212/WNL.0000000000008168
DP  - 2019 Sep 24
TA  - Neurology
PG  - e1312--e1323
VI  - 93
IP  - 13
4099  - http://n.neurology.org/content/93/13/e1312.short
4100  - http://n.neurology.org/content/93/13/e1312.full
SO  - Neurology2019 Sep 24; 93
AB  - Objective To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD).Methods An open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4–<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity.Results Oral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0–mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy.Conclusions Daily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study.Classification of evidence This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.BMI=body mass index; CINRG=Cooperative International Neuromuscular Research Group; CTCAE=Common Terminology Criteria for Adverse Events; DMD=Duchenne muscular dystrophy; DNHS=Duchenne Natural History Study; NF-κB=nuclear factor-κB; NSAA=North Star Ambulatory Assessment; SAE=serious adverse event; 6MWT=6-minute walk test; TEAE=treatment-emergent adverse event; TTRW=time to run/walk 10 m; TTSTAND=timed stand from supine