A new postmarketing registry, SKYCLARYS PASS (NCT06623890), will collect long-term safety and patient experience data on omaveloxolone (Skyclarys; Biogen), an FDA-approved treatment for Friedreich ataxia (FA). The registry aims to provide healthcare professionals with data to guide clinical decisions by following omaveloxolone-naïve patients for up to 5 years.
Study Design and Objectives
Presented at the 2024 International Congress for Ataxia Research (ICAR), the SKYCLARYS PASS is an observational, multicountry cohort registry expected to include around 300 omaveloxolone-naïve patients enrolled in the Freidreich’s Ataxia Global Consortium UNIFIED natural history study (UNIFAI). The primary objective is to assess long-term safety, focusing on the characterization of drug-induced liver injury (DILI) and congestive heart failure (CHF), which are considered potential risks associated with omaveloxolone.
Susan Perlman, MD, clinical professor of neurology at the David Geffen School of Medicine of UCLA, highlighted that secondary outcomes include treatment interruptions, discontinuations, and drug overdoses. The European Medicines Agency will receive an annual report, and the FDA will receive interim analyses of DILI and CHF adverse events (AEs).
Integration with Existing Studies
SKYCARYS PASS integrates data from the Friedreich Ataxia Clinical Outcome Measures Study (FACOMS) and the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS). FACOMS, established in 2004, includes over 1000 FA patients from Australia, Canada, India, New Zealand, and the USA. EFACTS, active since 2013, includes more than 1000 patients from various European countries.
Inclusion and Exclusion Criteria
The study includes patients with a documented diagnosis of FA confirmed via genetic testing, who are at least 16 years of age, omaveloxolone-naïve, and willing to comply with study visits. Exclusion criteria include prior enrollment in an omaveloxolone clinical trial, participation in a blinded interventional trial, and inability to comply with registry requirements.
Safety Assessments
DILI events are defined by Hy’s law criteria: total bilirubin levels at least twice the upper limit of normal (ULN) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels reaching three times ULN, or ALT/AST levels reaching ten times ULN. CHF events are defined as New York Heart Association (NYHA) class III or IV status, or death due to CHF, following the Standardized MedDRA Query (SMQ) for cardiac failure. Data on DILI and CHF, including descriptions and incidence rates, will be collected via AE and serious AE forms from baseline through 60 days after omaveloxolone discontinuation.
Exploratory Objectives
In addition to safety, the registry will explore health-related quality of life (HRQOL) and healthcare resource utilization using the FA-Health Index and the Modified Fatigue Impact Scale.
Omaveloxolone Dosage and Monitoring
Omaveloxolone, a nuclear factor-like 2 activator, was approved in 2022 as the first therapy for FA. The treatment label recommends 100 mg once daily, reduced to 50 mg once daily for moderate hepatic impairment or adverse reactions. It is not recommended for severe hepatic impairment. Monitoring ALT, AST, bilirubin, B-type natriuretic peptide, and lipid parameters is required before and during treatment.
