Good safety seen with FA drug Skyclarys over 1 year in real world
US study finds side effects of approved therapy are modest, manageable
The approved Friedreich’s ataxia (FA) drug Skyclarys (omaveloxolone) was found to be generally safe and well tolerated in people with FA in the real world, according to a new U.S. study that tested the medication’s safety over one year.
Most patients remained on Skyclarys for more than 12 months after starting treatment, and the side effects seen were “modest” and manageable, per the researchers. While some individuals experienced elevated liver enzymes, these were resolved with dose adjustments and decreased over time.
The researchers concluded that the safety profile observed in clinical practice in the real world closely resembles the favorable results seen in clinical trials — specifically those of MOXIe, a Phase 2 clinical trial (NCT02255435) that supported Skyclarys’ approval in the U.S. and Europe.
“These findings justify [Skyclarys’] ongoing use and suggest that the MOXIe study, as a representative clinical trial, reflects the effects in larger populations with [FA],” the researchers wrote.
The study, “Safety Monitoring of Omaveloxolone in Friedreich Ataxia: Results from One Year of Clinical Treatment,” was published in the journal Neurology and Therapy.
FA is caused by mutations in the FXN gene that impair the production of frataxin, a protein required for the proper function of mitochondria, which are cellular structures that produce most of the energy cells need to function. This leads to mitochondrial dysfunction and impairments in cell energy production — resulting in progressive neurodegeneration and a loss of muscle strength and coordination.
Skyclarys is the only treatment approved to date for FA in the U.S., and is indicated for adolescents and adults, ages 16 and older. It works by activating NRF2, a protein that regulates genes involved in mitochondrial function, antioxidant responses, and inflammation control. In doing so, the therapy is expected to slow or prevent disease progression among patients.
Drug safety profile investigated in real-world study
In this study, the researchers followed a total of 292 patients treated with Skyclarys after it became commercially available in the U.S. in June 2023. Among them, 40 had participated in the MOXIe trial.
“We followed patients over the first year of commercial availability, tracking laboratory values and reported adverse events,” the researchers wrote.
For 236 of the patients, treatment was prescribed at the Children’s Hospital of Philadelphia. This gave researchers access to more detailed information, allowing more comprehensive analysis. Among this cohort, or group of patients, nearly one-quarter — 63 individuals or 24% — experienced significant adverse events, particularly gastrointestinal issues, which affected 15%. Fatigue was seen for 3% and headache for 2.5%. These side effects generally eased within three months.
Most participants (88%) continued the treatment for at least one year. Among them, 85% reached the ideal maximum recommended dose of 150 mg/day, or three pills daily, while 14% were taking 100 mg/day, or two pills, and 1% were taking 50 mg/day, or one pill daily.
Five did not obtain approval for the treatment, three never initiated it, and 21 discontinued the treatment, mainly due to adverse events, or because they died for reasons unrelated to treatment, study data showed.
Noted side effects ‘diminished markedly over time’
During the first year of treatment, more than half of the participants (57%) experienced an elevation of transaminases, a type of liver enzyme, which remained elevated in 17% at the one-year time point. However, there were no significant changes in the levels of other markers of liver damage, including albumin and bilirubin.
“Few changes were noted in albumin or bilirubin, and such changes did not parallel changes in transaminases [liver enzymes], suggesting they are independent events,” the researchers wrote.
Treatment with Skyclarys did not change the levels of brain natriuretic peptide (BNP), a marker used to evaluate heart stress, and, the researchers noted, changes in cholesterol levels were small.
The safety features of [Skyclarys] after administration largely resemble the favorable features noted during clinical trials. … Overall, patients have responded well to commercial treatment with [Skyclarys].
A total of 27 patients paused dosing due to adverse events, but most — 23 in all — returned to treatment. Four people decided to permanently stop the medication.
“Abnormalities in serum liver function tests were limited to transaminases, resolved with dose pausing or reduction, and diminished markedly over time,” the researchers wrote.
Taken together, the findings showed that “the safety features of [Skyclarys] after administration largely resemble the favorable features noted during clinical trials,” the researchers wrote.
The team added: “Overall, patients have responded well to commercial treatment with [Skyclarys].”
However, more research is needed to better understand treatment efficacy after one year, the scientists noted. The team placed special emphasis on assessing changes in mFARS scores — a scale used by doctors to measure how FA affects a person’s movement, balance, and coordination.
Future studies should also look more closely at how the treatment may affect heart problems, which are common in people with this condition, the team noted.
