Agamree could reverse growth stunting in boys with Duchenne
Study suggests switching from standard steroids may help children grow taller
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Boys with Duchenne muscular dystrophy (DMD) may be able to regain lost height and overcome growth stunting by switching from traditional steroids to the newer medication Agamree (vamorolone), a new study suggests.
While standard corticosteroids are essential for managing DMD-related inflammation, they are known to halt bone growth in children. According to researchers, these new data suggest that corticosteroid-related growth stunting in DMD might be partly reversed by switching to Agamree in some cases.
The study, “Results of a phase II open-label, multiple-dose study of vamorolone (VBP15-006) in 7- to < 18-year-old boys with duchenne muscular dystrophy,” was published in the Journal of Neurology. The work was funded by Agamree’s current developer, Santhera Pharmaceuticals, and its former developer, Reveragen Biopharma.
The mechanics of corticosteroids
Corticosteroids work by binding to receptors for the stress hormone cortisol. This can help limit inflammation and preserve muscle strength for people with DMD, which is a genetic disorder marked by muscle weakness and wasting.
Agamree is known as a dissociative corticosteroid. It’s designed to bind to cortisol receptors in a way that retains the anti-inflammatory effects of traditional corticosteroids, but minimizes unwanted side effects. It is approved for DMD in the U.S., the U.K., the European Union, China, Hong Kong, and, most recently, Canada.
In this study, an international team of researchers including scientists at Santhera and Reveragen, reported on the outcomes from 34 boys with DMD, ages 7 to 17, who received long-term treatment with Agamree in clinical trials.
These boys initially participated in a three-month Phase 2 study (NCT05185622). After that, they all enrolled in an ongoing expanded access program (NCT03863119). At the time of the analyses conducted in this paper, most of the boys had been followed for more than a year in the expanded access program.
Before the Phase 2 study, 12 of the boys had not been on corticosteroids. In these boys, age-adjusted height scores remained generally stable over the course of follow-up. These data are consistent with other clinical trial data indicating that Agamree does not lead to growth stunting in children who have not previously been on traditional corticosteroids.
The other 22 boys had previously been on traditional corticosteroids, but switched to Agamree in the trials. In these children, age-adjusted height scores tended to increase over the course of follow-up, indicative of catch-up growth.
“There was no association between the duration of previous [corticosteroid] treatment and catch-up growth, suggesting that the negative effects of standard [corticosteroid] treatment on growth … may be at least partially reversible,” the researchers wrote.
In addition to effects on height, the researchers found that some of the boys experienced notable weight gain after starting Agamree. Weight gain is another common symptom associated with traditional corticosteroids.
Agamree-related weight gain tended to be most pronounced among previously-untreated patients who started on high doses of Agamree, though it was also seen in some boys who had previously been on other corticosteroids. The researchers called for further studies to evaluate why some DMD patients experience weight gain with Agamree while others do not.
“It would be beneficial to have a biomarker that predicts which individuals may be more prone to weight gain on long-term treatment, to potentially adjust diet and [Agamree] dose,” they wrote.
Study findings also showed that naturally produced cortisol levels tend to dip after patients start treatment with Agamree. According to researchers, these pharmacological findings have important implications for how to dose the therapy safely, especially in patients who have previously been on other corticosteroids. They emphasized the importance of following established dosing guidelines to avoid safety problems.
Overall, the data showed no new unexpected safety findings with Agamree, and the findings are broadly consistent with other studies suggesting Agamree can help reduce the risk of certain side effects associated with traditional corticosteroids.
