CHMP Gives Positive Opinion for Omaveloxolone as First Approved Treatment for Friedreich Ataxia in EU
In a phase 3 study, patients on omaveloxolone had less physical impairment compared with patients who received placebo, as measured by the modified Friedreich Ataxia Rating Scale.
Priya Singhal, MD, MPH
According to an announcement from Biogen, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has given a positive recommendation for omaveloxolone to be the first approved agent to treat patients with Friedreich ataxia (FA) in the EU. The therapy, which has already received FDA-approval, will continue to be marketed as Skyclarys if approved by the EMA.1
The European Commission (EC) will review omaveloxolone with a final decision expected in the first quarter of 2024. If approved, the therapy will be indicated for adults and adolescents with FA aged 16 years and older.
"The CHMP’s recommendation for SKYCLARYS is a significant milestone toward our goal of bringing a treatment that slows the progression of FA to the patient community in the region," Priya Singhal, MD, MPH, head of development at Biogen, said in a statement.1 "Upon approval of SKYCLARYS, we look forward to leveraging Biogen’s rare disease expertise and capabilities to bring this groundbreaking treatment to patients in the European Union living with this debilitating disease."
The CHMP’s positive opinion for omaveloxolone was based on efficacy and data from the placebo-controlled MOXIe Part 2 trial (NCT02255435). In the supporting trial data, treatment with the therapy resulted in statistically significant lower modified Friedreich Ataxia Rating Scale (mFARS) scores relative to placebo at week 48, accounting for a placebo-corrected difference between the groups of –2.41 points (P = .014; n = 82).2
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MOXIe was a 2-part study that included 2 placebo-controlled parts and an open-label extension (OLE). Part 1 was a placebo-controlled, dose-ranging study that enrolled 69 individuals, whereas part 2 was a multicenter, randomized, placebo-controlled clinical trial that enrolled 103 patients at 11 study sites in the US, Europe, and Australia. The OLE enrolled 149 patients and remains ongoing.
To evaluate the persistence of omaveloxolone’s treatment effect, investigators performed a delayed-start analysis comparing the difference in mFARS scores at the end of the 48-week placebo-controlled period with the difference after 72 weeks in the OLE. Using noninferiority testing, results showed that the difference in mFARS between omaveloxolone and placebo observed at the end of the placebo-controlled MOXIe part 2 (–2.17 [±1.09] points) was preserved after 72 weeks in the extension (–2.91 [±1.44] points). In addition, patients previously randomized to omaveloxolone in MOXIe part 2 continued to show no worsening in mFARS relative to their extension baseline through 144 weeks.3
FA, a rare neuromuscular disorder, is characterized by mitochondrial dysfunction, impaired NrF2 signaling, and decreased energy production. Omaveloxolone, a potent activator of Nrf2, restores mitochondrial function ex vivo in fibroblasts from patients with the disease. When it was approved in the US, the treatment label indicated a recommended dosage of 100 mg once daily for individuals with moderate hepatic impairment, to be further reduced to 50 mg once daily in the instance of adverse reactions. For those with severe hepatic impairment, the treatment is not recommended.4
