Early Duchenne drug trial points to motor gains in very young boys

A small clinical trial suggests that treating Duchenne muscular dystrophy in very young boys, before the usual age of diagnosis, may improve motor function. The findings matter because muscle damage in DMD begins early, while standard anti-inflammatory treatment often starts only after symptoms are clear.

The Phase II open-label study, published in Neurology, tested vamorolone in 20 steroid-naive boys ages 2 to 4 with DMD, according to Binghamton University. Participants received either 2 mg/kg/day or 6 mg/kg/day for 12 weeks, and most later continued treatment for about two years through an expanded access program.

Researchers reported that the drug was generally well tolerated and was linked to dose-dependent gains in motor function. They also found no apparent impairment of growth, though some children had weight gain and adrenal suppression, especially at the higher dose.

Why earlier treatment is being studied

Duchenne muscular dystrophy is a progressive genetic disease that causes loss of dystrophin, a protein needed by muscle tissue, Binghamton University said. As the disease advances, muscle is gradually replaced by scar tissue, making later repair harder than early protection.

Eric Hoffman, a professor of pharmaceutical sciences and associate dean for research and research development at Binghamton University’s School of Pharmacy and Pharmaceutical Sciences, said the damaging process in muscle starts at birth even though signs are often not recognized until early school age. He said current international care standards suggest corticosteroids after symptoms appear, but the biology indicates that may miss an earlier treatment window.

Binghamton University said DMD is the second-most common genetic disease worldwide after sickle cell anemia. The disease is tied to a gene on the X chromosome, so boys are mostly affected, and Binghamton said it occurs across racial, ethnic and socioeconomic groups.

What the trial found

The study examined safety, tolerability, growth, drug absorption and clearance, motor function, bone and metabolic biomarkers, and ease of administration, according to Binghamton University. Earlier studies of vamorolone had focused on children ages 4 to 7 after symptoms were already present; this trial specifically studied children younger than 4.

Hoffman said researchers were surprised by the speed of improvement in gross motor skills among children receiving the higher dose. According to Binghamton University, healthy peers have a normalized Bayley III gross motor score of 10, while the boys with DMD began at about five and improved to eight after 12 weeks on higher-dose vamorolone.

The researchers reported no serious adverse events and no treatment discontinuations. They cautioned, however, that vamorolone does not remove all steroid-related risks, even if it may reduce some of the side effects seen with traditional corticosteroids such as prednisone and deflazacort.

Traditional corticosteroids can cause growth stunting, weight gain, adrenal suppression and other long-term complications, Binghamton University said. Hoffman said clinicians and families have been reluctant to start those drugs in very young children because of those risks, while vamorolone has shown a more favorable growth profile.

Preliminary evidence

Vamorolone was developed by Hoffman and Kanneboyina Nagaraju, dean and professor of pharmaceutical sciences at Binghamton University’s pharmacy school, and received U.S. Food and Drug Administration approval in 2023 for DMD treatment, according to the university. Binghamton said the drug also has approvals in China, the European Union and the United Kingdom.

The study was not double-blind or placebo-controlled, so the findings need confirmation in stronger trials. Hoffman also noted that the U.S. Department of Health recently added DMD to the Recommended Universal Screening Panel for newborn screening, which could identify infants before symptoms if the early-treatment evidence holds up.

This story draws on original reporting from Medical Xpress.