Skyclarys benefiting many patients in real-world use, doctor finds
Neurologist giving treatment to about 300 people says most note less progression
Since its 2023 launch as the first and — to date — only approved treatment for Friedreich’s ataxia in the U.S., Skyclarys (omaveloxolone) has benefited most patients by either slowing or stopping disease progression.
David Lynch, MD, PhD, who directs the Friedreich’s Ataxia Program at the Children’s Hospital of Philadelphia, has started about 300 patients on Skyclarys, and “about 50% will tell you that something is better,” he said in a written Q&A with Friedreich’s Ataxia News.
A loss of muscle control marks the disease, and this can manifest as difficulties in everyday activities. Patients using Skyclarys are reporting helpful changes in “speech, typing, texting, sometimes walking and almost always fatigue,” Lynch said.
“Maybe 40% say that nothing is clearly better, but they haven’t progressed at all for the first time. And about 10% say no benefit,” added Lynch, a neurologist and a lead investigator in the clinical program for Skyclarys. “So in daily life about 90% note some difference, particularly in less progression.”
Skyclarys, approved for patients ages 16 and older, may help younger ones
Friedreich’s ataxia usually is more severe and faster progressing in people with onset at younger ages. But Lynch shared data at the International Congress for Ataxia Research (ICAR), held last month in the U.K., showing that Skyclarys may slow disease progression regardless of age at disease onset, a distinction he set as before or after 15 years old. (Skyclarys’ approval covers patients starting at age 16.)
This finding, he noted, comes from MOXIe (NCT02255435), a Phase 2 clinical trial that supported Skyclarys’ approval in the U.S., and later in the European Union, marketed by Biogen. Supportive data also comes from comparisons among up to 2,000 patients worldwide, ages 4 to 80, taking part in FA-COMS (NCT03090789), a long-term and observational natural history study aiming to expand disease research and care.
Neurological function, measured using the modified Friedreich’s Ataxia Rating Scale (mFARS), improved significantly after three years of treatment with Skyclarys compared with matched patients in the natural history study, regardless of a patient’s age when symptoms manifested.
“When broken into those with age of onset before 15 and those after age 15, both groups improved. The amount of improvement was slightly more in those with earlier onset but the difference was small. So essentially, any Friedreich’s ataxia patient may get better on [Skyclarys],” Lynch wrote.
BOLD trial evaluating treatment’s safety in young children
A Phase 1 clinical study, called BOLD (NCT06054893), is underway to define the best dose of Skyclarys for use in younger patients. This trial, at Children’s Hospital of Philadelphia, may still be enrolling up to 20 children and adolescents with Friedreich’s ataxia, ages 2 to 15.
In addition to accessing pharmacokinetics — how Skyclarys moves into, through, and out of the body after a single dose — BOLD will test the oral medication’s safety over up to 240 weeks, or about 4.6 years, of use. It does not include measures examining how well Skyclarys works in younger patients.
“The study is designed to define the right dose in children and to define preliminary safety — it is not constructed to assess efficacy. Still, because subjects will remain on drug for an extended period of time, there will be signals that tell us about benefit,” Lynch said.
Registry study looking into safety over up to 5 years of treatment
A poster presented at ICAR also describes the design of SKYCLARYS PASS (NCT06623890), a post-approval registry to profile the Skyclarys’ long-term safety in about 300 patients, ages 16 and older, prescribed the treatment in real-world settings. The registry, also noting changes in Skyclarys’ use among enrolled patients for up to five years, “is just rolling out now,” Lynch said.
Its main focus will be monitoring changes in liver and heart function, a safety-related request from the U.S. Food and Drug Administration. Initial findings may be available in a year or two, Lynch said.
“The aspect being investigated is not whether [Skyclarys] produces side effects, but whether it is protective or not,” Lynch said. Participants in MOXIe “had so little heart disease” that effects on the heart could not be evaluated, he added, and SKYCLARYS PASS, together with a study undertaken by Lynch’s team, is looking to address this knowledge gap.
Data from the MOXIe trial’s second part, evaluating the treatment’s best dose (150 mg daily) as determined in its first part, showed that gastrointestinal changes and elevations in liver enzymes after starting on Skyclarys were mild to moderate in severity, and transient. They were “time limited — they went away over the 12 weeks of the original study,” Lynch said. This would be “consistent with a metabolic effect, not a toxicity event,” he noted.
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