Skyclarys reduces inflammation marker in adults with FA
Italian real-world study finds lower IL-6 levels, stable disease scores
Skyclarys (omaveloxolone) was well tolerated and associated with stable disease measures and reduced inflammation markers in adults with Friedreich’s ataxia (FA) over about six months, according to a real-world study in Italy.
In particular, the treatment was associated with significantly lower levels of interleukin (IL)-6, a molecule involved in inflammation. “An interesting point of novelty of this study is a significant reduction in IL-6 levels starting at 12 weeks and lowering at 24 weeks … supporting a possible immunomodulatory effect of [Skyclarys] in adult [FA] patients,” the researchers wrote.
The study, “Early experience on omaveloxolone in adult patients with Friedreich’s ataxia: a real-world observational study,” was published in the Journal of Neurology.
Understanding Friedreich’s ataxia and how Skyclarys works
FA is caused by mutations in the FXN gene that lead to reduced production of frataxin, a protein essential for the function of mitochondria, the cell’s energy production centers. Muscle and nerve cells are especially vulnerable to low energy levels, which can lead to FA symptoms such as poor coordination and balance (ataxia), muscle weakness, and other neurological problems.
Skyclarys, an approved oral therapy for FA, is designed to activate nuclear factor erythroid 2-related factor 2 (Nrf2), a protein that supports mitochondrial function, boosts antioxidant defenses, and helps limit inflammation.
To better understand how Skyclarys performs in a real-life setting, researchers conducted a single-center observational study in 20 adults with FA treated at the University Hospital P. Giaccone of Palermo, in Italy. Most participants were women, had a mean age of 40.6, and had been living with FA for an average of nearly 25 years.
Participants received Skyclarys at a dose of 150 mg/day and were followed for 24 weeks (about six months). During follow-up visits, researchers assessed disease status using several standardized tools: the modified Friedreich’s Ataxia Rating Scale (mFARS) to track disease progression, the FA Activities of Daily Living (FA-ADL) scale to evaluate everyday functioning (such as speech, eating, walking, and self-care), and the Scale for the Assessment and Rating of Ataxia (SARA) to measure ataxia severity.
Over the follow-up period, participants showed no signs of clinical worsening, as mFARS, FA-ADL, and SARA scores remained stable compared with baseline. Levels of IL-6 fell significantly after about three and six months of treatment, dropping from 4.1 to 2.8 picograms/mL.
The researchers also observed trends toward lower levels of creatine phosphokinase, a marker of muscle damage, and of C-reactive protein, a marker of inflammation.
Exploring biomarkers and treatment response
Further analysis suggested that levels of CPK and NT-proBNP, a marker linked to heart stress, differed between patients who did and did not respond to Skyclarys treatment. A treatment response was defined as a reduction of 2.5 points on the mFARS scale.
However, when multiple variables were considered together in a multivariate analysis, no single factor emerged as a significant predictor of response to Skyclarys. “However, the short duration, and the small sample size limit the generalizability of the results,” the researchers wrote.
Additional analysis showed that changes in mFARS scores were significantly associated with longer treatment exposure, while FA-ADL scores were correlated with baseline IL-6 levels.
This “might suggest that a longer follow-up could highlight a measurable clinical improvement,” the researchers wrote.
Treatment was generally well tolerated, and no patients discontinued Skyclarys during the follow-up period. The most common adverse events were temporary and asymptomatic increases in liver enzyme levels and heartburn.
According to the researchers, the short treatment duration and the small number of patients limit the generalizability of the results. “Further multicentre studies with prolonged follow-up are needed to gather clinical experiences with [Skyclarys] in [FA],” the team wrote.
