At Binghamton University, researchers were among the first to find ways to help patients of Duchenne muscular dystrophy (DMD), with the development of an effective drug. Now, they are continuing that work, looking to reduce its effects even earlier.
Since DMD is a progressive disease, the muscles of those suffering will gradually be replaced by scar tissue. It is one challenge to keep muscle as muscle, but reversing scar-tissue damage is an entirely other and much more complicated goal. Instead, treating DMD at a young, presymptomatic - even newborn - age may have the best chance of most dramatically helping those affected.
"We have known for some time that the destructive processes in muscle in a DMD boy start from birth, even though symptoms are not typically recognized until early school years," said Eric Hoffman, professor of pharmaceutical sciences and associate dean of research and research development at the School of Pharmacy and Pharmaceutical Sciences. "International standard of care suggests initiating anti-inflammatory corticosteroids after symptoms are evident, but the science says that this might already be too late."
The breakthrough
Vamorolone, a drug developed by Hoffman and Kanneboyina Nagaraju, professor of pharmaceutical sciences and dean of the School of Pharmacy and Pharmaceutical Sciences, received Food and Drug Administration (FDA) approval in 2023 for the treatment of patients with DMD. This was the first drug to receive approval for DMD throughout the world, including in China, the European Union, and the United Kingdom.
DMD is the second-most common genetic disease worldwide, after sickle-cell anemia, and leads to the loss of the dystrophin protein in muscle tissues, resulting in progressive weakness. The gene that controls the disease has the highest new mutation rate and is the largest in the human genome, and because it is on the X chromosome, young boys are mostly those affected, though it is indiscriminate to race, ethnicity, or socioeconomic status.
"DMD has long been recognized as one of the most important genetic diseases worldwide, both due to its relatively high frequency, as well as the devastating progressive clinical course," Nagaraju said.
The future of therapy
Today, Hoffman is working to improve upon the treatment and further prove that this drug is effective at younger ages. A recent Phase II open-label study published in Neurology evaluated vamorolone in 20 steroid-naive boys aged 2 to <4 years with DMD. Participants received either 2 mg/kg/day or 6 mg/kg/day for 12 weeks, with most continuing treatment for roughly two years in a follow-up expanded access program.
Previous clinical studies of vamorolone had focused on children aged 4-7 years after symptoms first appeared; this was the first study specifically examining children younger than 4 years old.
This 12-week treatment study included 19-20 participants who then entered a long-term Expanded Access Program (EAP) of about two years. During the study, researchers assessed the safety and tolerability of the drug, growth (via height, weight, and BMI), pharmacokinetics (how the drug is absorbed and cleared from the body), motor function, bone and metabolic biomarkers, and ease of administration.
"The clinical and patient family communities are resistant to starting traditional corticosteroid anti-inflammatories at such young ages due to extensive stunting of growth, severe mood disturbances, and other side effects," Hoffman said. "Vamorolone is a corticosteroid with an improved safety profile, including no stunting of growth, so it may hold promise in young pre-symptomatic infants and young boys."
The main conclusion of the study showed that vamorolone was generally well tolerated, with dose-dependent improvements in motor function, and it did not appear to impair growth, although some children experienced weight gain and adrenal suppression, particularly at the higher dose. The traditional corticosteroids, such as prednisone and deflazacort, often cause growth stunting, weight gain, adrenal suppression, and other complications in long-term use.
"We were surprised at the rapid improvement of gross motor skills in the DMD children on the higher dose of vamorolone," Hoffman said. "Healthy peers have a normalized Bayley III gross motor skill score of 10, while the DMD boys before treatment had about half this score, consistent with previous studies. Twelve weeks of vamorolone treatment improved the score from five at baseline to eight of 10 after treatment."
The researchers also found safety was generally favorable, with no serious adverse events or treatment discontinuations. However, while vamorolone may improve some steroid side effects, it does not eliminate them. This study was also not a double-blind placebo-controlled trial, so the findings are considered preliminary.
"The U.S. Department of Health just recently added DMD to the Recommended Universal Screening Panel (RUSP) for newborn screening of all babies in the United States. Hopefully, vamorolone may become an option for these babies if these preliminary data are confirmed," Hoffman added.
