Omaveloxolone

NeurologyLive's Friday 5 highlights: 1) David Lynch on omaveloxolone's long-term safety for Freidreich ataxia. 2) Andy Berkowski on 2024 RLS guidelines changes. 3) MS and domestic violence challenges. 4) Rebecca Edelmayer on Alzheimer's blood biomarkers. 5) Shared decision-making for NMOSD therapies.

FDA approved omaveloxolone (Skyclarys; Biogen) in 2023 as the first treatment for Friedreich ataxia (FA), based on phase 3 MOXIe Part 2 trial data. Long-term analysis at the International Congress at Ataxia Research 2024 showed it to be safe and well-tolerated, with treatment-emergent adverse events (TEAEs) subsiding over time. David Lynch, MD, PhD, recommends gradual dosage titration to manage metabolic effects.

At the 2024 ICAR, the SKYCLARYS PASS registry (NCT06623890) was presented to collect long-term safety and patient experience data on omaveloxolone, an FDA-approved treatment for Friedreich ataxia. The registry will follow 300 omaveloxolone-naïve patients for up to 5 years, focusing on potential risks like drug-induced liver injury and congestive heart failure, with annual reports to the European Medicines Agency and FDA interim analyses. The study also explores health-related quality of life and healthcare resource utilization.

The phase 3 MOXIe Part 2 trial analysis of omaveloxolone (Skyclarys) for Friedreich ataxia (FA) showed most treatment-emergent adverse events (TEAEs) occurred within the first 12 weeks, with gastrointestinal disorders and aminotransferase elevations (AST/ALT) being the most common. Elevated AST/ALT occurred in 29.4% of omaveloxolone-treated patients within the first 12 weeks and 9.8% after 12 weeks, compared to only 1 case in the placebo group. The median time for side effects to appear was shorter in the omaveloxolone group, with a median duration of elevated ALT and AST of 33 days. The study concluded that these findings guide patient treatment expectations and emphasize the importance of dosing compliance.

Kwa and Kendal examine ethical issues in treating Friedreich’s ataxia, including resource allocation, balancing benefits and risks of gene therapies, and informed consent. They highlight barriers to equitable access, such as high costs and strict eligibility criteria, emphasizing the need for transparent, accessible healthcare strategies in precision medicine.

PTC Therapeutics plans to submit a New Drug Application to the FDA for vatiquinone, its oral therapy for Friedreich’s ataxia, based on positive results from the MOVE-FA trial and extension studies, despite missing the primary goal. Vatiquinone showed significant benefits in upright stability and a strong safety profile, particularly relevant for pediatric patients.

Larimar presented positive early clinical results for nomlabofusp (CTI-1601), a drug designed to correct frataxin deficiency in FRDA patients. The phase 1 study involved 55 patients, with primary endpoints of safety and tolerability. A phase 2 trial showed increased frataxin levels with doses of 25 mg and 50 mg. An ongoing open-label extension study will include adolescents and children, with preliminary data expected in Q4 2024. Larimar aims for accelerated FDA approval with a BLA submission planned for mid-next year.

Biogen Canada's omaveloxolone, a potential treatment for Friedreich's ataxia, has been accepted for priority review by Health Canada, offering hope for patients with this rare, progressive neuromuscular disease.

Recent review highlights advancements in Friedreich’s ataxia (FRDA) therapy, including the approval of Skyclarys (omaveloxolone) and emerging gene therapies, emphasizing the need for sensitive outcome measures and personalized medicine approaches.