Biogen begins BRAVE trial testing Skyclarys in FA children ages 2-15
Therapy approved for patients 16 and older, but disease typically begins earlier
Biogen has initiated dosing in a Phase 3 clinical trial, called BRAVE, that’s testing the oral therapy Skyclarys (omaveloxolone) among children with Friedreich’s ataxia (FA) ages 2 to 15.
Skyclarys already is approved in the U.S. and the European Union, among other locations, for FA patients ages 16 and older. It is the first and only approved treatment for the inherited disease.
However, the first signs of FA in patients are often seen much earlier — between the ages 5 and 15 — though symptoms can also develop later in life.
“Recognizing the symptoms of Friedreich ataxia typically begin in childhood, and earlier onset of symptoms is associated with faster disease progression, there is tremendous unmet need in the pediatric community,” Stephanie Fradette, head of the neuromuscular development unit at Biogen, said in a company press release, which noted that the trial is expected to enroll more than 250 children worldwide.
“We have been urgently advancing the pediatric development plan for omaveloxolone [Skyclarys] and are thrilled that the Phase 3 BRAVE study has now begun,” Fradette said.
FA is caused by mutations in the FXN gene that result in deficiencies in the production of the protein frataxin. This protein is essential for the function of mitochondria, which are the structures in cells responsible for energy generation. Without proper mitochondrial function, nerve and muscle cells — which have high energy demands — may experience damage. This typically leads to symptoms such as lack of muscle coordination, muscle weakness, impaired speech, and difficulty swallowing.
Skyclarys aims to slow or prevent FA progression by promoting mitochondrial function, boosting antioxidant responses, and preventing inflammation. It activates a protein called nuclear factor erythroid 2-related factor 2 (NrF2), whose signaling is impaired in people with FA.
No treatments available for FA patients younger than 16
Susan Perlman, MD, the director of the Ataxia Center at the David Geffen School of Medicine at UCLA and a professor of neurology, noted that treatment options, such as Skyclarys, are needed for pediatric FA patients, for whom no therapies are yet available.
“Early onset patients often have the most aggressive and fast progressive form of Friedreich ataxia and through the BRAVE study we aim to determine the potential safety and efficacy of [Skyclarys] for children living with the disease,” Perlman said.
Globally, Biogen anticipates enrolling about 255 children with a genetically confirmed diagnosis of FA in the BRAVE study (NCT06953583). One site in Virginia is currently recruiting, with other locations in the U.S. expected to join. Locations in Australia, Brazil, and Canada, and across Europe, also anticipate beginning enrollment after alignment with regulators and ethics committees. The Biogen Trial Link will also be providing updated information about the study.
The goal of BRAVE is to assess the safety, efficacy, and pharmacological properties of the therapy in this younger patient population.
Early onset patients often have the most aggressive and fast progressive form of Friedreich ataxia and through the BRAVE study we aim to determine the potential safety and efficacy of [Skyclarys] for children living with the disease.
The first part of the trial will test Skyclarys’ effectiveness for one year, primarily looking at changes in Upright Stability Score, a part of the modified FA rating scale (mFARS) that measures sitting posture, stance, heel-to-toe walking, and gait. Two-thirds of participants will be randomly selected to receive Skyclarys, with the remainder on a placebo for comparison.
After 52 weeks (one year), the study will proceed to an open-label extension, in which all participants will receive Skyclarys for up to 104 weeks, or two years. According to Biogen, this will allow the researchers to better understand the therapy’s longer-term effects. Other endpoints, or goals, include evaluating changes in overall health, heart health, and the process of puberty.
FA community input helped BRAVE trial design
Biogen noted that investigators, medical experts, and members of the FA community all contributed to the design of the trial.
“We are immensely grateful for the input from the entire FA community that has helped shape the design of this important study,” Fradette said.
Regulatory approval of Skyclarys was supported by results from the MOXIe clinical trial (NCT02255435). The therapy, taken daily as oral capsules, was found to significantly benefit neurological function among the trial’s participants. On the mFARS scale, which measures disease progression, 48 weeks, or nearly one year, of treatment led to a 2.4-point improvement compared with a placebo.
More recently, a real-world U.S. study reported positive safety and tolerability results, resembling the findings seen in clinical trials.
About the Author
