Omaveloxolone (Skyclarys), the first FDA-approved treatment for Friedreich ataxia (FA), continues to demonstrate a consistent safety and efficacy profile, according to recent analyses presented at the International Congress at Ataxia Research (ICAR) 2024. These findings reinforce the drug's role in managing this rare, inherited neurodegenerative disorder caused by mutations in the FXN gene, which leads to reduced frataxin production, a protein crucial for mitochondrial function.
Long-Term Safety and Tolerability
Data from the MOXIe trial extension and supportive studies indicate that omaveloxolone is generally safe and well-tolerated. According to David Lynch, MD, PhD, a principal investigator in the MOXIe trials, the long-term safety data revealed no new concerning issues beyond the initially observed gastrointestinal side effects (nausea and diarrhea in 10-15% of patients), headaches, and transient elevations in hepatic transaminase levels. These transaminase changes typically resolve without abnormalities in liver function, suggesting a metabolic rather than toxic effect.
Efficacy Across Age Groups
An analysis of the MOXIe trial data, stratified by age of onset (early vs. late), demonstrated that omaveloxolone was effective in both groups. While specific benefits varied slightly, the overall efficacy was comparable, reinforcing the concept that restoring NRF2 activity can benefit different Friedreich ataxia patient subtypes. It's important to note that omaveloxolone is not currently approved for patients under 16, but a clinical trial is underway to determine appropriate dosing for this age group, given the drug's dose-dependent efficacy.
SKYCLARYS PASS Registry
The SKYCLARYS PASS registry (NCT06623890), a collaborative effort with the worldwide Unify natural history study, will monitor patients on omaveloxolone for five years to evaluate its long-term safety and effectiveness in real-world settings. This registry aims to identify rare side effects and their frequency, as well as provide insights into the drug's performance in patients who may not have met the inclusion criteria for the original clinical trials due to factors like travel or mobility limitations. Initial data from post-marketing use align well with clinical trial results, suggesting the trial outcomes are reliable predictors of real-world results.
Managing Adverse Events
Clinicians can mitigate gastrointestinal adverse events by initiating treatment with a lower dose and gradually increasing it over two to six months, allowing most patients to eventually tolerate the full 150 mg dose. Similarly, elevated transaminase levels can be managed by slowly increasing the dose. These elevations are typically not associated with abnormalities in albumin or bilirubin and usually resolve within one to six months.
Clinical vs. Real-World Care
While clinical trials provide controlled, standardized data, real-world clinical care allows for individualized treatment approaches. The focus shifts from mFARS score changes to assessing whether the patient is genuinely improving in their daily life. This holistic approach provides a more comprehensive understanding of omaveloxolone's value as a treatment that helps people manage Friedreich ataxia.
