Friedreich's Ataxia Treatment Shows Extended Benefit

Richard Mark Kirkner

September 21, 2021

Dr David Lynch

Omaveloxolone, an activator of the protein Nrf2 that protects against inflammation, has shown a potentially beneficial effect in slowing the progression of Friedreich's ataxia out to more than 2 years, according to results of a clinical trial presented as a late-breaking abstract at the International Congress of Parkinson's Disease and Movement Disorders.

The study, labeled the Delayed-Start Study, is an extension study of the two-part MOXIE phase 2 trial of omaveloxolone.

"This study shows two things," said David Lynch, MD, PhD, of Children's Hospital of Philadelphia. "It doesn't matter when you started omaveloxolone for you to see a benefit; and that the benefit that the active group saw in the first part of the study was maintained as they went into the delayed-start part. So in fact omaveloxolone does modify the long-term behavior of the disease."

Friedreich's ataxia only affects about 22,000 people worldwide, and children typically present between the ages of 5 and 15, Lynch said.

The extension study included 73 patients who completed either of the first two parts of the MOXIe trial. The MOXIe trial randomized patients on a 3:1 basis to either omaveloxolone 2.5-300 mg or placebo for 12 weeks in the first part. The second part was a double-blind trial of 103 patients randomized on a 1:1 basis to 150 mg omaveloxolone or placebo for 48 weeks. Participants had a baseline modified Friedreich's ataxia scale (mFARS) of 20-80 and were aged 16-40 years.

Patients in the extension study did not have severe pes cavus. The extension study was a 72-week evaluation of patients who were in either the treatment or placebo groups in the first two parts. There was a 4-week off-treatment period between the end of MOXIe part 2 and the beginning of the extension study, in which all patients received omaveloxolone.

At the end of the placebo-controlled study, patients taking omaveloxolone showed a –2.18-point (±0.96) difference in improvement in mFARS score (P = .027), compared with the placebo group, which was preserved at the end of the delayed-start period, with a –2.92-point (±2.13) improvement (P = .179), Lynch said.

In the extension study, former placebo patients who went on omaveloxolone had annualized mFARS slopes similar to the previously treated patients – 0.29 (±0.68) and 0.17 (±0.61), respectively (P = .85) – from weeks 48 to 144, Lynch said.

"This study showed that, when analyzed in a delayed-start fashion, it does not matter when you start omaveloxolone to see a benefit: Each cohort benefited almost equally once they started the drug," Lynch said in an interview. "Also, in both groups, once they started omaveloxolone, they changed slower than people in natural history studies."

A Clinically Meaningful Difference?

Reached for comment, Massimo Pandolfo, MD, a neurologist at McGill University, Montreal, noted that the Delayed-Start Study included only patients without pes cavus, an indication that the patients had less severe disease. "It would be important to see how overall patients with Friedreich's ataxia would have responded to the medication without this kind of selection," Pandolfo said in an interview.

He also noted that the seemingly modest improvement in mFARS score could be an issue. "It's a very difficult question: What is a clinically meaningful difference in this kind of rating scale? I would argue that probably 2 points is not a huge difference by itself, but it may be meaningful and one indicator of that is that if it was accompanied by also a significant difference in activities of daily living scale."

In any event, Pandolfo said this is the first medication for Friedreich's ataxia that has "survived" a randomized clinical trial.

Lynch said the study sponsor, Reata, may prepare a new drug application for omaveloxolone in patients ages 16 and older. "That would leave a need for investigation in younger FA patients."

Lynch disclosed that his institution receives a grant from trial sponsor Reata to conduct the MOXIe trial. Pandolfo reports financial relationships with Design Therapeutics, Exicure and Voyager Therapeutics.

This article originally appeared on, part of the Medscape Professional Network.


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