Study Could Herald New Treatment for Muscular Dystrophy

Scientists focus on deflazacort

New research from the University of Rochester has shown that the corticosteroid deflazacort is a safe and effective treatment for patients with Duchenne muscular dystrophy (DMD). The findings, published in Neurology, could pave the way for the first U.S.-approved treatment for the disease, according to the investigators.

DMD is a condition found almost exclusively in boys. The disease is characterized by muscle weakness, which appears at a young age and progresses rapidly, leading to significant disability. Boys with DMD often end up in a wheelchair by age 9 or 10 because of weakness in their legs. The symptoms eventually spread to other parts of the body, including the heart and the muscles responsible for breathing, and the disease is often fatal by the time the individual reaches his late teens. An estimated 28,000 people in the U.S. have the disease.

While there is currently no approved treatment for DMD in the U.S., the corticosteroid prednisone is often used “off label” to treat the condition. Several studies have shown that daily use of corticosteroids can increase muscle mass and slow muscle degeneration in DMD patients, thereby prolonging their ability to walk and preserving respiratory function. However, many DMD patients in the U.S. are not prescribed corticosteroids, primarily because of concern over the adverse effects of prolonged drug use in children.

Deflazacort is approved for use in Europe and elsewhere to treat DMD, but the drug has never gone through the FDA’s approval process. Studies of the drug abroad have shown that it is effective and has fewer adverse effects compared with other corticosteroids, especially less weight gain, according to the authors.

Deflazacort was the subject of a phase 3 trial in the U.S. in the mid-1990s. However, soon after the study was completed, the company sponsoring the research lost interest in the drug; the study results were never published; and efforts to obtain FDA approval were abandoned.

Lead author Robert Griggs, MD, and others spent decades attempting to gain access to the original study data. In the intervening years, another company––Marathon Pharmaceuticals––acquired the rights to the deflazacort and began a new push to gain FDA approval for the drug. The researchers were never able to obtain the data from the original clinical trial sponsor and had to reconstruct the results from the information collected at each individual study site. These data form the basis for the Neurology article.

The study, which involved 196 DMD patients, showed that deflazacort was safe, that it effectively preserved muscle strength, and that it was associated with less weight gain compared with prednisone. These data provided the basis for two new drug applications currently pending before the FDA for use of the drug to treat DMD. If approved, deflazacort with be the first drug sanctioned in the U.S. to treat the disease.

Griggs is also leading another international study that addresses the variation in care that DMD patients currently receive by establishing a universal standard of care. The new study, called FOR-DMD (Finding the Optimum Regimen of Corticosteroids for Duchenne Muscular Dystrophy), will determine whether daily steroid treatment or an alternative regime is more effective in slowing disease progression and in managing adverse events. The study, which will evaluate both deflazacort and prednisone, will follow 200 patients for three to five years.

Source: University of Rochester Medical Center; September 8, 2016.