By Anna Shavers
On February 28th, the U.S. Food and Drug Administration approved SKYCLARYS, the first drug ever to treat Friedreich’s ataxia, following a multisite clinical trial that included the University of Florida, UF Health and the Norman Fixel Institute for Neurological Diseases.
Considered the most common genetic cause of ataxia, Friedreich’s ataxia affects one in every 50,000 people in the United States – many of whom are children – according to the National Institutes of Health. With its FDA approval, SKYCLARYS became the first ever approved drug to show a positive result in slowing the progression of Friedrich’s ataxia.
“The FDA approval represents a milestone for developing a therapy for a disease that does not always receive recognition because Friedreich’s ataxia is considered ‘rare’,” said Sub Subramony, M.D., professor of neurology at the University of Florida College of Medicine and neurologist at the Fixel Institute and the site principal investigator (PI) for the study at UF. “Being ‘rare’ should not take away from the severity and impact this disease has on the lives of patients. In addition, the National Organization of Rare Disorders finds that one in 10 Americans has some form of rare disease. Thus, this approval brings hope for a similar outcome in many such diseases.”
Friedreich’s ataxia typically begins around the age of ten years and causes a loss of coordination, muscle weakness, fatigue and more. The symptoms of Friedreich’s ataxia often progress and become more serious as the person ages. Many patients lose control of physical movements, become wheelchair bound or develop heart issues.
“Currently there are no approved therapies for any of the genetic ataxias, and clinicians often make a care plan for the patient that addresses individual symptoms and that hopefully provides them a better quality of life,” said Matthew Burns, M.D., Ph.D., assistant professor of neurology at the University of Florida College of Medicine and neurologist in the ataxia clinic at the Norman Fixel Institute for Neurological Diseases at UF Health. “It’s encouraging to see a new drug specifically for Friedreich’s ataxia that could reduce disease progression.”
The recently approved drug, SKYCLARYS, showed promise in the Phase 2 MOXIe trial for slowing the progression of Friedreich’s ataxia. The placebo-controlled, randomized, double-blinded trial tested the use of SKYCLARYS over a 48-week period.
Results showed participants that received SKYCLARYS saw a slowing of disease progression based on a significantly slower increase in the primary endpoint measure of neurological decline, the modified Friedreich’s Ataxia Rating Scale (mFARS), compared to the placebo group.
The mFARS, originally developed by Dr. Subramony, assesses a patient’s ability to perform several aspects of neurological function, such as standing, walking, or speaking and increasing score reflects worsening of the disease.
Additional analyses of the data from the MOXIe trial, including data from the open label extension and matching of trial participants with selected subjects in a natural history study appear to further support the results of the data from the placebo-controlled phase.
SKYCLARYS is designed to activate a protein called Nrf2, which is important for the health of mitochondria, which are impaired in people living with Friedreich’s ataxia. SKYCLARYS supports the activation and boosts the activity of the Nrf2 protein, leading to an improvement in patients’ ability to perform daily life activities.
Once the drug becomes available to the public, UF Health physicians will work with patients and families to discuss the risks and benefits and how to gain access.
“We are excited to see how this may impact and help people with Friedreich’s ataxia live with a better quality of life than before,” said Dr. Subramony.
The MOXIe clinical trial and subsequent research and analysis was conducted by several members of the Collaborative Clinical research Network in Friedreich Ataxia (CCRN FA) in the US which is supported by the Friedreich Ataxia Research Alliance (FARA) together with added centers in Europe and Australia. Dr David Lynch at Children’s Hospital of Philadelphia is the PI of the CCRN FA.
The research was funded by Reata Pharmaceuticals, maker of SKYCLARYS.
Dr. Subramony has received research support from Reata Pharmaceuticals, PTC therapeutics, Retrotope, Biohaven, Biogen, Avidity Biosciences, Fulcrum therapeutics, AAVANTI Bio and RENEO pharma; he is also supported by grants from FDA, NIH, MDA, Wyck Foundation, FSHD Society, National Ataxia Foundation and FARA. He has served on advisory boards for Reata, Fulcrum therapeutics, Avexis, Stealth therapeutics and Dyne therapeutics.