Abstract
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.
Glossary
- 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
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was funded by NIH National Institutes of Neurologic Disorders and Stroke R44 NS095423.
Class of Evidence: NPub.org/coe
- Received October 26, 2018.
- Accepted in final form May 29, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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